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A Long-Term Study for Participants Previously Treated With Ciltacabtagene Autoleucel.
- NCT05201781
To collect long-term follow-up data on delayed adverse events after administration of cilta-cel, and to characterize and understand the long-term safety profile of cilta-cel.
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Participants who have received at least one dose of cilta-cel in a Company-sponsored clinical study
- Participants who have provided informed consent for this study
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 1 First in Human Study of ARV-393 in Adult Participants with Advanced Non-Hodgkins Lymphoma.
- NCT06393738
Primary Objective:
To evaluate the safety and tolerability of ARV-393, determine MTD if necessary, and identify the RP2D(s) and dosing schedule.
Secondary Objective:
- To characterize the pharmacokinetic profile of ARV-393 in plasma,
- To assess the preliminary anti-tumor activity of ARV-393.
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Protocol Number:
012406
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Principal Investigator:
Matthew Matasar
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Phase:
Early Phase I
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
ARV-393
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Eligible participants aged ≥18 years.
- Have relapsed/refractory mature B-cell non-Hodgkin lymphoma (NHL) and ≥2 prior systemic therapies, or histologically confirmed AITL that has recurred or progressed following institutional standard-of-care therapy.
- Participants must also have ≥1 measurable lesion at study entry
- Eastern Cooperative Oncology Group performance status of 0 or 1,
- Freshly biopsied or archival tumor tissue available,
- Participants with adequate organ function,
- Participants must accept and follow pregnancy prevention guidance.
Exclusion Criteria:
- No prior allogeneic stem cell transplant or solid organ transplantation, Autologous stem cell transplant, must not have occurred ≤100 days, previous CAR T-cell therapy ≤60 days, radiotherapy ≤ 2 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, prior to ARV-393 treatment initiation.
- Participants must not have significant acute or chronic medical illness, including hypereosinophilic syndrome, active interstitial lung disease or pneumonitis, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
- Participants with an inability to comply with listed prohibited treatments.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 1 Open-Label, Multi-Center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT-200 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML), or with Relapsed/Refractory, High/Very High Risk Myelodysplastic Syndrome (MDS).
- NCT04666688
The primary objectives are:
- To establish the safety and tolerability of LYT-200 as a single agent
- To recommend the dose or doses of LYT-200 for Phase 2 (R2PD)
- To determine the incidence of DLTs during Cycle 1 (28 days) across dose levels
The secondary objectives are:
- To determine the preliminary efficacy of LYT-200 as a single treatment
- To characterize the PK profile of LYT-200
The exploratory objectives are:
- To study pharmacodynamic markers, including immunological and molecular changes in the peripheral blood and bone marrow and serum gal-9
- To assess the immunogenicity of LYT-200
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Protocol Number:
022204
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Principal Investigator:
Dale Schaar
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Phase:
Phase I
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Scope:
National
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Applicable Disease Sites:
Myeloid and Monocytic Leukemia
,Other Hematopoietic
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
LYT-200
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
Part 1 1. Written Informed Consent (mentally competent patient, able to understand and willing to sign the informed consent form) 2. Age ≥ 18 years, male or non-pregnant female 3. Able to comply with the study protocol, as per Investigator's judgment 4. Histologically confirmed, unresectable locally advanced or metastatic cancer. There are no limits to prior lines of therapies received for the treatment of the cancer condition for which the patient is being enrolled into this study. 1. For the Part 1 combination urothelial carcinoma Cohorts 13 and 14: histologically or cytologically confirmed diagnosis of unresectable, locally advanced or metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra (i.e., transitional cell carcinoma). 2. For the Part 1 combination H/N cancer Cohorts 11 and 12: histologically confirmed, locally advanced or metastatic squamous cell carcinoma of head and neck (SCCHN; oral cavity, oropharynx, hypopharynx, or larynx). 5. For urothelial and H/N combination cancer cohorts, prior exposure to immunotherapy is allowed, with standard of care treatment options and/or within a clinical trial context. If the patient received an anti-PD-1 and/or an anti-PD-L1 containing regimen at any point, they must have demonstrated at least stable disease, as per RECIST 1.1 or iRECIST criteria to one of these treatment regimens, if these measurements are available. If RECIST or iRECIST measurements are not available, then clinical PFS of at least 4 months is required to have been achieved on any of the prior anti-PD-1 and/or anti-PD-L1 containing regimens. 6. There is no PD-L1 expression requirement for the Part 1 combination urothelial and H/N cohorts; however, fresh biopsy or archival tissue is required for assessment of PD-L1 by IHC, or a historical PD-L1 expression by IHC must be available. If PD-L1 expression data are already available, this does not override the protocol preference for obtaining a fresh biopsy whenever feasible. 7. For Part 1 combination cohort H/N cancer patients of oropharynx origin: human papilloma virus (HPV) status needs to be established in the screening period or at any point while patient is on study drug, unless it is historically known. p16+ as a surrogate for HPV+, HPV RNA ISH or DNA PCR are all acceptable. The study accepts both HPV+ and HPV- patients. 8. Life expectancy > 3 months according to Investigator's judgment 9. ECOG performance status 0-1 10. Patient able and willing to undergo pre- and on/post treatment biopsies. According to the Investigator's judgment, the planned biopsies should not expose the patient to substantially increased risk of complications. Every effort will be made that the same lesion is biopsied on repeat biopsies. If the patient is eligible according to all other criteria but declines to consent to a biopsy or there are other medical reasons precluding biopsy, this will be discussed with the Sponsor. 11. Measurable disease, according to RECIST v1.1. Note that lesions intended to be biopsied should not be target lesions. 12. Adequate hematologic and end organ function, defined by the following laboratory results obtained prior to first dose of study drug treatment, provided no anticancer treatment was administered within the last 7 days: 1. neutrophil count ≥ 1 x 109/L 2. platelet count ≥ 100 x 109/L; for hepatocellular carcinoma (HCC) in Part 1 ≥ 50 x 109/L 3. hemoglobin ≥ 9.0 g/dL without transfusion in the previous week 4. creatinine ≤ 1.5 x the upper limit of normal (ULN); or eGFR > 50 mg/mmol 5. aspartate aminotransferase AST (SGOT) ≤ 3 x ULN (≤ 5 x ULN when HCC or hepatic metastases are present) 6. alanine aminotransferase (ALT [SGPT]) ≤ 3 x ULN (≤ 5 x ULN when HCC or hepatic metastases present) 7. bilirubin ≤ 1.5 x ULN (patients with known Gilbert's disease may have a bilirubin ≤ 3.0 x ULN) 8. albumin ≥ 3.0 g/dL 9. international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN, unless patient receiving anticoagulant therapy 13. No evidence of active serious infection or infections requiring parenteral antibiotics. 14. Women of childbearing potential must have a negative pregnancy test within 72 h prior to start of treatment. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 180 days after the last study treatment. A woman is of childbearing potential if she is post-menarche, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists. 15. Four (4) weeks or 5 half-lives (whichever is shorter) since the last dose of anticancer therapy before the first LYT-200 administration 16. Bisphosphonate treatment (e.g., zoledronic acid) or denosumab are allowed if previously used prior to commencement of clinical trial. 17. Patients: 1. who have already received at least one prior line of systemic therapy for metastatic or locally advanced disease, and/or 2. who have a tumor type for which there are no available standard of care options 18. Patients who have not previously received a gemcitabine-containing regimen
Exclusion Criteria
1. Patient unwilling or unable to follow protocol requirements 2. Patient diagnosed with metastatic cancer of an unknown primary 3. Current illicit drug addiction (medical and recreational marijuana/cannabidiol [CBD]/ tetrahydrocannabinol [THC] would not be considered "illicit") 4. Clinically significant, active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease). Prophylactic or therapeutic use of anticoagulants is allowed. 5. Pregnant and/or lactating females 6. Receiving any other investigational agents or participating in any other clinical trial involving another investigational agent for treatment of solid tumors within 3 weeks or 5 half-lives of the administered drug (whichever is shorter) prior to the first dose of study drug, or major surgery or planned surgery within 4 weeks of the first dose of study drug (this includes dental surgery). 7. Radiation therapy within 4 weeks of the first dose of study drug, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass, and which does not jeopardize required measurable lesions for response assessment (RECIST v1.1). 8. Patients with fungating tumor masses 9. History or current evidence of any condition, therapy, any active infections, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator 10. Grade 4 immune-mediated toxicities with a prior checkpoint inhibitor. Grade 2 or Grade 3 pneumonitis or any other Grade 3 checkpoint inhibitor-related toxicity that led to immunotherapy treatment discontinuation. Low-grade (< Grade 3) toxicities, such as neuropathy from prior treatments, manageable electrolyte abnormalities and lymphopenia, alopecia and vitiligo are allowed. 11. History of other prior or other concomitant malignancy that requires other active treatment. 12. Active parenchymal brain metastases, patients with carcinomatous meningitis or leptomeningeal metastases. Patients with brain metastases are eligible provided they have shown clinically and radiographically stable disease for at least 4 weeks after definitive therapy and have not used steroids (> 10 mg/day of prednisone or equivalent) for at least 4 weeks prior to the first dose of study drug 13. Evidence of severe or uncontrolled systemic diseases, congestive heart failure > New York Heart Association (NYHA) class 2, myocardial infarction (MI) within 6 months, or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial 14. Any medical condition that the Investigator considers significant to compromise the safety of the patient or that impairs the interpretation of LYT-200 toxicity assessment 15. Serious non-healing wound, active ulcer, or untreated bone fracture unless for e.g., a rib fracture for (which does not elicit treatment) 16. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. For the purposes of this study, "recurrent" is defined as ³ 3 drains in the last 30 days 17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 18. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of Cycle 1, Day 1 19. History of pulmonary embolism, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1 20. Active autoimmune disorder (except type I/II diabetes, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia areata). 21. Requires systemic immunosuppressive treatment, including, but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents. Patients who have received or are receiving acute, low dose systemic immunosuppressant medications (e.g., ≤ 10 mg/day of prednisone or equivalent) may be enrolled. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy [e.g., ≤ 10 mg/day of prednisone equivalent] for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone), topical steroids, intranasal steroids, intra-articular, and ophthalmic steroids is allowed. 22. Severe tumor-related pain (Grade 3, CTCAE v.5.0) unresponsive to broad analgesic interventions (oral and/or patches) 23. Hypercalcemia (defined as ³ Grade 3, per CTCAE v 5.0) despite use of bisphosphonates 24. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk of treatment complications 25. Received organ transplant(s) 26. Patients undergoing dialysis 27. For Part 1, hormonal androgen deprivation therapy is allowed to continue for patients with metastatic castration-resistant prostate cancer 28. Any ablative therapy (Radio Frequency Ablation or Percutaneous Ethanol Injection) for HCC < 6 weeks prior trial entry 29. Hepatic encephalopathy or severe liver adenoma 30. Child-Pugh score ≥ 7
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 1 Study to Assess Safety and Tolerability of REGN5837, an Anti-CD22 x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination with Odronextamab, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients with Aggressive B-Cell Non-Hodgkin Lymphomas (ATHENA-1)
- NCT05685173
The primary objective of the study is:
- To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine
RP2D regimen(s) (defined as either a MTD regimen or a lower dose regimen) of
REGN5837 in combination with odronextamab in patients with relapsed or refractory
aggressive B-NHL.
The secondary objectives of the study are:
- To evaluate the pharmacokinetics (PK) of REGN5837 when given in combination with
odronextamab
- To evaluate the PK of odronextamab when given in combination with REGN5837
- To assess the immunogenicity of REGN5837 and odronextamab
- To assess the preliminary anti-tumor activity of REGN5837 in combination with
odronextamab in patients with relapsed or refractory aggressive B-NHL
The exploratory objectives of the study are:
- To evaluate the association between clinical efficacy and safety with biomarkers of
systemic immune activation (serum cytokine levels, T-cell counts and activation
markers)
- To evaluate the association between disease response and/or relapse and the change
from baseline in the count and phenotype of tumor-infiltrating T cells and tumor B cell
target antigen (CD20, CD22) expression
- To evaluate association of the molecular Minimal Residual Disease (MRD) status in
patients with a clinical CR with progression-free survival (PFS) and OS
- To assess other biomarkers (pharmacodynamic, predictive, and prognostic) potentially
related to REGN5837 in combination with odronextamab exposure, anti-tumor
activity, and safety
- To evaluate the relationships among pharmacodynamics, drug concentrations, and
clinical safety and efficacy measure
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Protocol Number:
012303
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Principal Investigator:
Matthew Matasar
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Phase:
Phase I
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy multiple agents systemic
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Drugs Involved:
Odronextamab(REGN1979)
REGN5837
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Read Inclusion & Exclusion Criteria
Key Inclusion Criteria:
1. Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent, as described in the protocol. 2. Measurable disease on cross sectional imaging as defined in the protocol 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Adequate bone marrow, renal and hepatic function as defined in the protocol 5. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed 6. During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participant has an accessible lesion that can be biopsied without significant risk to the participant.
Key Exclusion Criteria:
1. Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab 2. Diagnosis of mantle cell lymphoma (MCL) 3. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS lymphoma, as described in the protocol 4. Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter, as described in the protocol 5. Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol 6. Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab 7. Co-morbid conditions, as described in the protocol 8. Infections, as described in the protocol 9. Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicaseNOTE: Other protocol defined inclusion / exclusion criteria apply
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of DSP- 5336 in Adult Acute Leukemia Patients with and without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation.
- NCT04988555
Phase 1: Dose-Escalation Objectives:
Primary Objectives:
- To assess the safety and tolerability of DSP-5336 in adult patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia of ambiguous lineage.
- To determine the recommended Phase 2 dose (RP2D) of DSP-5336 based on the lowest dose of DSP-5336 that provides the maximum biologic and clinical effect, or the maximum tolerated dose (MTD), whichever is lower.
Secondary Objectives:
- To characterize the PK profiles of DSP-5336, including the PK profile in the presence of concomitant use of selected azoles, ie, posaconazole, voriconazole, fluconazole, or isavuconazonium (prodrug of isavuconazole).
- To evaluate the preliminary clinical activity of DSP-5336 in adult patients with AML, ALL, or acute leukemia of ambiguous lineage
- To determine the cardiac safety of DSP-5336 administered as a single agent by 12-lead safety and intensive ECG monitoring, and in the presence of azoles by 12-lead safety ECG monitoring
Exploratory Objectives:
- To assess minimal residual disease (MRD) status
- To assess the pharmacodynamic effect of DSP-5336
- To explore the PK exposure-response (ie, safety, efficacy, or biomarkers) relationship
- To identify the metabolite profile of DSP-5336 in plasma samples
- To identify potential biomarkers capable of predicting clinical efficacy and/or toxicity of DSP-5336
Phase 2: Dose-expansion objectives:
Primary Objective:
- To evaluate the clinical activity of DSP-5336 in adult patients with relapsed/refractory AML who have MLLr and/or NPM1m* by investigator assessment
Secondary Objectives:
- To evaluate the clinical activity of DSP-5336 by central assessment
- To further assess the safety and tolerability of DSP-5336
Exploratory Objectives:
- To assess MRD status
- To further assess the pharmacodynamic effect of DSP-5336
- To identify potential biomarkers capable of predicting clinical efficacy and/or toxicity of DSP-5336
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Protocol Number:
022303
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Principal Investigator:
Neil Palmisiano
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Phase:
Phase I/II
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Scope:
National
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Applicable Disease Sites:
Leukemia, other
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
DSP- 5336
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Read Inclusion & Exclusion Criteria
Inclusion Criteria
1. Patients in the Phase 1 dose-escalation portion must have a diagnosis of relapsed or refractory AML, ALL or acute leukemia of ambiguous lineage, as determined by pathology review at the treating institution, and who failed available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage. Enrollment to the phase 1 portion of the study may be limited to patients with certain genetic abnormalities. Patients in the Phase 2 dose-expansion portion must have a confirmed diagnosis of relapsed or refractory AML, as determined by pathology review at the treating institution, and who failed available standard therapies known to be active for their AML. They must also have a documented KMT2A (MLL)-fusion or NPM1 mutation, which includes those with coexisting FLT3 genomic alterations and/or IDH1/2 mutations. 2. Be > 18 years of age or 20 years if required by local regulation 3. ECOG < 2 4. WBC below 30,000/μL (hydroxyurea allowed prior to initiation of the study treatment) 5. Clearance of creatinine (CLcr) level ≥ 50 ml/min, assessed by the Cockcroft-Gault formula 6. Total bilirubin ≤1.5 the upper limit of normal (ULN) (or ≤2.0 ULN for patients with known Gilbert's syndrome) 7. Aspartate aminotransferase (AST) ≤3.0 times ULN 8. Alanine aminotransferase (ALT) ≤3.0 times ULN 9. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia or neuropathy. 10. Be willing to attend study visits as required by the protocol 11. Have an estimated life expectancy ≥3 months, based on the investigator's assessment 12. Females of childbearing potential must have a negative serum pregnancy test. Females of childbearing potential are defined as women who have (1) experienced menarche and have not undergone sterilization procedures (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or have (2) not experienced menopause (defined as having amenorrhea continuously for more than 12 months that is not determined to be drug-induced, or who are taking hormone replacement therapy with serum follicle-stimulating hormone > 35 mlU/ml). 13. Must agree to use a combination of 2 or more different contraception methods (oral contraceptives/implantable hormonal contraceptives*, and barrier method*) or use prevention of pregnancy measures (ie, agreement to refrain completely from heterosexual intercourse) during the study and for 6 months (for females and males alike) after the last dose of study drug, if male or female patient of child-producing potential 14. Have AML/ALL material suitable for genomic analysis of AML or ALL genetic alterations
Exclusion Criteria:
1. Has a left ventricular ejection fraction (LVEF) <45%, as determined by ECHO 2. Histological diagnosis of acute promyelocytic leukemia 3. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP 5336 4. Has had abnormal ECGs that are clinically significant, such as QT prolongation (QTc >450 msec for males and >470 msec for females, with QTc corrected according to Fridericia's formula [QTcF]) 5. Has an active, uncontrolled, bacterial, viral, or fungal infection requiring systemic therapy 6. Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole and itraconazole. Other antifungals that are used as standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor. 7. Received immunotherapy, including tumor vaccines and checkpoint inhibitors, within 42 days prior to the first dose of DSP-5336 8. Has been on other investigational treatment within the previous 4 weeks prior to the first dose of DSP-5336 9. Had major surgery within 28 days prior to the first dose of DSP-5336 10. Has active central nervous system leukemia 11. Previously received menin-MLL inhibitors 12. Has immediately life threatening or severe complications of leukemia 13. Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336 14. Received a donor lymphocyte infusion within 28 days prior to the first dose of DSP-5336, or receiving immunosuppressive therapy post-HSCT at the time of screening, or with clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD 15. Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) within 14 days prior to the first dose of DSP-5336 16. Received anthracycline where cumulative doses exceeded the upper limit per the label approved in each country or investigator discretion (if there is no label restriction, investigator must state the cumulative dose received for each patient and sign to indicate that, in his/her medical opinion, stated prior dose of the agent does not put patient at undue risk of anthracycline-related cardiotoxicity 17. In the opinion of the treating investigator, have any concurrent conditions that could pose an undue medical hazard or interfere with interpretation of study results; these conditions include, but are not limited to: clinically significant non-healing or healing wounds; concurrent congestive heart failure; concurrent unstable angina; concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation); recent (within the prior 6 months) myocardial infarction; acute coronary syndrome within the previous 6 months; significant pulmonary disease (shortness of breath at rest or on mild exertion), eg, due to concurrent severe obstructive pulmonary disease, concurrent hypertension not controlled with concomitant medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 6 months 18. Have an active acute or chronic infection, including human immunodeficiency virus (HIV) as determined by anti-HIV antibodies; and hepatitis B virus (HBV) or hepatitis C virus (HCV) as determined by hepatitis B surface antigen (HBsAg) or anti-HCV antibodies, respectively. For sites in Japan only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs) antibody test should be performed if HBsAg is negative. If HBc antibody or HBs antibody test is positive, HBV DNA quantification test should be performed to confirm that HBV DNA is negative. 19. Have advanced liver disease or cirrhosis (Child-Pugh's Class B or greater) 20. Have one or more active autoimmune diseases requiring immunosuppressive therapy other than low-dose corticosteroids (equivalent to prednisone 10mg daily) or azathioprine. Patients on stable immunomodulatory medications may be considered by the investigator 21. Have active (uncontrolled, metastatic) malignancies of another type 22. Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication 23. Have cognitive, psychologic, or psychosocial impediment that would impair the ability of the patient o receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures 24. Are pregnant or breastfeeding or planning to become pregnant Note: Patients who are breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose of any study drugs and do not feed the baby with breast milk expressed after receiving the first dose of any study drugs. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug 25. Have any history or complication of interstitial lung disease (for sites in Japan only) 26. Have a history of Torsades de Pointes
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 1b Multicenter, Open-label, Study of JNJ-90014496, an Autologous CD19/CD20 Bi-specific CAR-T Cell Therapy in Adult Participants with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma.
- NCT05421663
The primary objectives are to assess the safety and tolerability of JNJ-90014496 and to determine the recommended Phase 2 dose(s) (RP2D[s]).
The secondary objectives are to evaluate the preliminary efficacy of JNJ-90014496 in participants with r/r B-NHL and to characterize JNJ-90014496 PK in blood.
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Protocol Number:
012316
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Principal Investigator:
Joanna Rhodes
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Phase:
Phase I
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
JNJ-90014496
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent
- Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive
- Must meet the following indications for each subtype: Relapsed or refractory mature aggressive large B cell non-Hodgkin lymphoma (NHL) and follicular lymphoma Grade 3b: Participants must have had >= 2 lines of systemic therapy or >= 1 line of systemic therapy in case of participants ineligible for high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT); Relapsed or refractory follicular lymphoma Grade 1-3a and marginal zone lymphoma: Participants must have had >= 2 prior lines of anti-neoplastic systemic therapy. Participants also must have prior exposure to an anti-CD20 monoclonal antibody
- Frontline high-risk diffuse large B Cell lymphoma (DLBCL): Participants must have DLBCL or high-grade B-cell lymphoma (HGBCL) with residual lymphoma by positive interim positron emission computed tomography 2 or 3 cycles of frontline chemoimmunotherapy. Participants must have only received 2 or 3 cycles of frontline chemoimmunotherapy for DLBCL
- Measurable disease as defined by Lugano 2014 classification
- Eastern cooperative oncology group (ECOG) performance status of either 0 or 1. ECOG of 0 to 2 is allowed in frontline high-risk DLBCL cohort
Exclusion Criteria:
- Diagnosis of Human herpes virus (HHV) 8-positive DLBCL or T cell/histiocyte-rich large B-cell lymphoma
- Any prior solid organ or allogeneic stem cell transplantation
- Autologous stem cell transplant within 12 weeks of chimeric antigen receptor (CAR) T cell infusion
- Uncontrolled active infections
- History of deep vein thrombosis or pulmonary embolism within six months of infusion (except for line associated deep vein thrombosis [DVT])
- History of stroke, unstable angina, myocardial infarction, congestive heart failure New York Heart Association (NYHA) Class III or IV, severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening
- History of a seizure disorder, dementia, cerebellar disease or neurodegenerative disorder
- Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
- Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones)
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 2 Study of Inotuzumab Ozogamicin in Children and Young Adults with Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL).
- NCT02981628
Primary Aim:
To determine the morphologic response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) following one cycle of treatment with InO in children with relapsed or refractory CD22+ B-ALL.
1.2 Secondary Aims:
1.2.1 To determine the CR/CRi rate following 2 cycles of InO therapy.
1.2.2 To determine the safety of single agent InO administered at the adult
recommended phase 2 dose (RP2D) to pediatric patients with relapsed or
refractory CD22+ B-ALL.
1.2.3 To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients.
1.2.4 To determine the incidence, severity, and outcomes of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver in patients during InO therapy and following subsequent treatment, including myeloablative hematopoietic stem cell transplantation (HSCT).
1.2.5 To estimate the 3-year event-free survival (EFS), 3-year overall survival (OS), and among responders, duration of CR/CRi for pediatric patients with relapsed or refractory B-ALL treated with InO.
1.3 Exploratory Aims:
1.3.1 To assess the level of CD22 surface expression and CD22 site density on leukemic blasts and correlate with clinical outcomes after treatment with InO.
View All Details
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Protocol Number:
111707
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Principal Investigator:
Archana Sharma
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Phase:
Phase II
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Scope:
National
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Applicable Disease Sites:
Lymphoid Leukemia
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
Inotuzumab ozogamicin (CMC-544)
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Patients must be >= 1 year and < 22 years of age at the time of enrollment
- Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
- NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
- Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
- Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin [PE] is strongly recommended)
- In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
- Patients with one of the following:
- Second or greater relapse;
- Primary refractory disease with at least 2 prior induction attempts;
- First relapse refractory to at least one prior re-induction attempt
- Any relapse after HSCT (Cohort 1 ONLY)Patients with Down syndrome are eligible ONLY for Cohort 1 with:
- Any of above disease status, OR
- First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
- Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
- A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
- A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
- >= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, >= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
- Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.
- Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
- Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
- Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
- Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
- Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
- Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
- 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
- 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
- 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
- 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
- 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
- Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
- Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
- Patients with any prior history of SOS irrespective of severity
- Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
- Patients who have been previously treated with inotuzumab ozogamicin
- Patients who have previously received HSCT (Cohort 2 only)
- Patients with Down syndrome (Cohort 2 only)
- History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
- Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
- Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
- Patients who are currently receiving another investigational drug
- Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
- Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
- Patients who are currently receiving or plan to receive corticosteroids except as described below
- Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
- Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
- Patients who have an active uncontrolled infection defined as:
- Positive bacterial blood culture within 48 hours of study enrollment;
- Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
- A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
- Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
- Active viral or protozoal infection requiring IV treatment
- Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
- There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
- Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
- Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
- Lactating females are not eligible unless they agree not to breastfeed their infants
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 2 Study of SNDX-5613 in Combination with Chemotherapy for Patients with Relapsed or Refractory KMT2A-Rearranged Infant Leukemia.
- NCT05761171
The primary objective on MRD negative remission rate. It is anticipated that approximately 4 to 12 patients in the safety phase could be evaluable for the primary efficacy endpoint. The additional patients needed to address the primary efficacy endpoint will be enrolled at the selected RP2Ds in the expansion phase.
The primary objective on MRD negative remission rate. Assuming a 10% ineligible/inevaluable rate, 24 eligible patients with R/R infant KMT2A-R ALL patients may be enrolled to meet this target accrual. This includes the patients with R/R infant KMT2A-R ALL enrolled at RP2D-L and RP2D-M in the safety phase who receive at least one dose of SNDX-5613.
View All Details
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Protocol Number:
112402
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Principal Investigator:
Richard A Drachtman
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Phase:
Phase II
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Scope:
National
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Applicable Disease Sites:
Leukemia, other
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Therapies Involved:
Chemotherapy single agent systemic
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Drugs Involved:
SNDX-5613
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Patients must be 1 month to < 6 years old at the time of study enrollment and must have had initial diagnosis of leukemia at < 2 years old.
- Patients must have KMT2A-rearranged acute lymphoblastic leukemia (ALL), acute leukemia of ambiguous lineage (ALAL), or mixed phenotype acute leukemia (MPAL), which is determined to be refractory or in first marrow relapse. All patients must undergo cytogenetics and fluorescence in situ hybridization (FISH) testing of a relapsed/refractory blast sample at a Children's Oncology Group (COG)-approved laboratory for KMT2A-R status determination and the presence of a KMT2A- rearrangement must be confirmed by central review. Cytogenetics results must be submitted for central review by Day 10 of protocol therapy, for confirmation of KMT2A-R status. Patients enrolled with refractory disease may utilize initial diagnostic cytogenetics for eligibility and submission for central review if testing was performed at a COG approved laboratory. Patients will be eligible to remain on protocol therapy if KMT2A-R is confirmed by central review. Additional methods of assessing for KMT2A-R may be considered if FISH does not detect the rearrangement.
- Disease status at time of enrollment must be one of the following:
- First relapse (untreated): Any recurrence of marrow disease, with or without other extramedullary sites(s), at any point after achieving remission ("remission-1", per definition below) and meeting one of the below criteria. Patients must not have received any disease-directed therapy for the marrow relapse prior to enrollment, other than permitted cytoreduction.
- Relapse M1: M1 morphology (< 5% blasts) + at least 2 confirmatory tests showing >= 1% blasts (testing includes flow, cytogenetics, polymerase chain reaction [PCR]ext-generation sequencing [NGS] of immunoglobulin [Ig]/T-cell receptor [TCR] rearrangement, and/or PCR or NGS of fusion gene identical to diagnosis), OR
- Relapse M2: M2 morphology (5-25% blasts) + 1 confirmatory test showing > 1% blasts, OR
- Relapse M3: M3 morphology (> 25% blasts)
- Primary refractory, or failure to achieve remission-1: remission-1 is defined as < 1% marrow blasts by flow MRD and resolution of extramedullary disease following at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted
- Central nervous system (CNS) disease: Patients must have CNS1 or CNS2 status and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy.
- Patients with CNS3 disease may receive antecedent intrathecal chemotherapy to achieve CNS1 or CNS2 status prior to enrollment.
- Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of CNS disease prior to enrollment.
- White blood cell (WBC) must be < 50,000/uL at the time of study enrollment. Patients can receive cytoreduction with hydroxyurea and/or corticosteroids for up to 7 days prior to enrollment.
- Patients >= 12 months of age must have a performance status by Lansky Scale of >= 50%.
- Patients must be able to take enteral medications. Acceptable routes of administration for revumenib (SNDX-5613) include: oral (PO), nasogastric (NG) tube, nasojejunal (NJ) tube, nasoduodenal (ND), and gastrostomy tube (G-tube).
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
- >= 14 days must have elapsed after the completion of other cytotoxic therapy, including patients who relapse during pre-Maintenance upfront therapy, with these specific exceptions: cytoreduction with hydroxyurea and/or corticosteroids, and intrathecal chemotherapy, which have no required washout periods. For patients who relapse during upfront Maintenance therapy, >= 7 days must have elapsed after the last dose of chemotherapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
- NOTE: Cytoreduction with hydroxyurea and/or corticosteroids is permitted prior to enrollment for patients with WBC >= 50,000/uL, and by provider discretion regardless of WBC, to reduce potential risk of differentiation syndrome with revumenib initiation. Hydroxyurea and/or corticosteroids may be given for up to 7 days, with no wash-out required.
- NOTE: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy that is given up to 7 days prior to the initiation of protocol therapy counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given > 7 days prior does not count as protocol therapy.
- NOTE: Prior exposure to fludarabine and cytarabine (FLA) is permitted.
- Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent.
- Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
- Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or >= 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
- Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon, or cytokines
- Stem cell infusions (with or without total body irradiation (TBI):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or stem cell boost: >= 84 days after infusion
- Donor leukocyte infusion: >= 28 days
- Cellular therapy: >= 28 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 84 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow radiation.
- A creatinine based on age as follows:
- Age 1 month to < 6 months: maximum creatinine 0.4 mg/dL
- Age 6 months to < 1 year: maximum creatinine 0.5 mg/dL
- Age 1 to < 2 years: maximum creatinine 0.6 mg/dL
- Age 2 to < 6 years: maximum creatinine 0.8 mg/dL OR
- a 24-hour urine creatinine clearance >= 70 mL/min/1.73 m^2 OR
- a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
- NOTE: Estimated GFR (eGFR) from creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
- A direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, unless disease related
- Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3 x ULN) unless disease related.
- Note: For the purpose of eligibility, the ULN for SGPT (ALT) has been set to the value of 45 U/L
- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram.
- Corrected QT interval using Fridericia formula (QTcF) of < 450 msec (using the average of triplicate measurements)
- NOTE: There are no specific electrolyte parameters for eligibility. However, it should be noted that, to limit QTc prolongation risk, patients must maintain adequate potassium and magnesium levels to initiate and continue revumenib (SNDX-5613) on protocol therapy.
- Patients must be able to comply with the safety monitoring requirements of the study, in the opinion of the treating investigator.
Exclusion Criteria:
- Patients with isolated extramedullary leukemia.
- Patients diagnosed with Down syndrome.
- Patients known to have one of the following syndromes:
- Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.
- Patients with a secondary KMT2A-R leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
- Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrollment.
- Patients with an active, uncontrolled infection, further defined below:
- Positive bacterial blood culture within 48 hours of study enrollment
- Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
- A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
- Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with Clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
- Active viral or protozoal infection requiring IV treatment
- Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of enrollment.
- Patients with active acute graft-versus-host disease (GVHD) > grade 0 (unless skin only), or chronic GVHD > mild (unless skin only) are not eligible. Patients with acute or chronic skin GVHD that is =< grade 1, or chronic skin GVHD that is graded as mild are eligible.
- Patients who have received a prior solid organ transplantation.
- Patients with known Charcot-Marie-Tooth disease, if treating on Regimen A (with vincristine).
- CYP3A4 Inhibitors or Inducers: Patients who require concomitant therapy with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers, as these are prohibited during the chemotherapy combination cycles. These agents should be discontinued at least 5 half-lives prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitor -azole antifungals are permitted during the revumenib (SNDX-5613) monotherapy cycles, with appropriate revumenib (SNDX-5613) dose modification
- P-glycoprotein (P-gp) inhibitors or inducers: Vincristine is a substrate for P-gp. Concomitant use of P-gp inhibitors or inducers with vincristine (patients receiving Regimen A Cycle 1) should be avoided.
- Investigational drugs: Patients who are currently receiving another investigational drug.
- Anti-cancer agents: Patients who are currently receiving other anti-cancer agents (exceptions: hydroxyurea and corticosteroids, which may be used as cytoreduction prior to enrollment).
- Anti-GVHD agents: Patients who are receiving cyclosporine, tacrolimus, or other systemic agents to treat graft-versus-host disease post bone marrow transplant. Patients should discontinue anti-GVHD agents > 7 days prior to enrollment and have no evidence of worsening GVHD. Topical steroids are permitted.
- Patients who have previously been treated with revumenib (SNDX-5613). Prior exposure to other menin inhibitors is permitted.
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA in Subjects with Multiple Myeloma.
- NCT04133636
To evaluate the overall minimal residual disease (MRD) negative rate of subjects who receive JNJ-68284528.
View All Details
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Protocol Number:
011909
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Principal Investigator:
Mansi R Shah
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Phase:
Phase II
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Scope:
National
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Applicable Disease Sites:
Multiple Myeloma
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Drugs Involved:
JNJ-68284528
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines
- Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or <=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT
- Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy
- Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation
- Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (>=) 5.5 milligrams per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 total copies) in at least 20 percent (%) of the total plasma cell population
- Cohort F:
- Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria
- Received initial therapy as specified below. The dose/schedule of cycles administered will be as per standard of care. It is acceptable for up to 1 cycle of the protocol-specified regimens to be missing one of the listed agents (example, held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of care or; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or quadruplet regimen
- Cohort G: Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: a) Ineligibility due to advanced age; or b) Ineligibility due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or c) Subject refusal of high-dose chemotherapy with ASCT as initial treatment
- Cohort H: Considered a candidate for high-dose chemotherapy with ASCT as initial treatment
- Cohorts A, B, C, E, G, H:
- Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligrams (mg)/24 hours
- Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
- Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)*1 cm is required
- Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria
- Cohorts A, B, C, D, E, F, G, H: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Exclusion Criteria:
- Cohorts A, B, D, F: Any therapy that is targeted to BCMA
- Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
- Cohorts A, B, C, D, F:
- Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
- Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis
- Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder
- Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
- Cohorts F, G, and H: Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: a) non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured; b) skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (N0M0): with a Gleason score of greater than or equal to (=>)6, treated within the last 24 months or untreated and under surveillance, with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence, e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence; f) malignancy that is considered cured with minimal risk of recurrence
- Cohorts E, G, and H: Frailty index of >= 2 according to Myeloma Geriatric Assessment score
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the
Efficacy and Safety of Golcadomide Plus R-CHOP Chemotherapy vs Placebo Plus R-CHOP
Chemotherapy in Participants with Previously Untreated High-risk Large B-cell Lymphoma
(GOLSEEK-1)
- NCT06356129
Primary:
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma with respect to PFS as assessed by the
Investigator.
Secondary (efficacy):
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma with respect to PFS as assessed by the IRAC.
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma with respect to OR as assessed by the
Investigator.
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma with respect to CMR as assessed by the
Investigator
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants
with untreated high-risk large B-cell lymphoma with respect to PFS24.
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants
with untreated high-risk large B-cell lymphoma with respect to DoR.
To evaluate the efficacy of treatment with golcadomide plus R-CHOP vs placebo-RCHOP
on overall survival in participants with untreated high-risk large B-cell lymphoma with respect to PFS2.
To evaluate the exposure of CHOP cytotoxic components (cyclophosphamide, doxorubicin,
vincristine) in golcadomide plus R-CHOP vs placebo plus R-CHOP in participants with
untreated high-risk large-B-cell lymphoma with respect to relative dose intensity (RDI).
To compare the disease symptoms, functioning, and overall HRQoL of golcadomide plus R-CHOP vs placebo-RCHOP in participants with untreated high-risk large B-cell lymphoma as measured by the EORTC QLQ-C30 and the FACT-LymS
Secondary (Safety):
To evaluate the safety of golcadomide plus RCHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma.
View All Details
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Protocol Number:
012407
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Principal Investigator:
Yun Kyoung Tiger
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Phase:
Phase III
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy multiple agents systemic
-
Drugs Involved:
Golcadomide
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Read Inclusion & Exclusion Criteria
Inclusion Criteria:
- Histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated large B-cell lymphoma (LBCL) according to 2022 world health organization (WHO) classification including:i) Diffuse large B-cell lymphoma (DLBCL), not otherwise specified [including germinalcenter B-cell (GCB) and activated B-cell (ABC) types]ii) High-grade B-cell lymphoma, with MYC and BCL2 rearrangements (HGBL-MYC/BCL2double-hit lymphomas)iii) High-grade B-cell lymphoma, not otherwise specifiediv) T-cell/histiocyte/rich large B-cell lymphoma (THRLBCL)v) Epstein-Barr virus + DLBCL
- International Prognostic Index (IPI) score 1 or 2 with lactate dehydrogenase (LDH) > 1.3 x upper limit of normal (ULN) and/or bulky disease defined as single lesion of ≥ 7 cm OR IPI ≥ 3.
- Measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and 1 bi-dimensionally measurable (> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification.
- Must have Ann Arbor Stage II-IV disease.
Exclusion Criteria:
- Any significant medical condition, active infection, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
- Any other subtype of lymphoma. Cases of primary mediastinal (thymic) large B-cell lymphoma (PMBCL), primary cutaneous DLBCL-leg type, Grade 3b FL, indolent lymphoma transformed to large B-cell lymphoma (LBCL), Anaplastic lymphoma kinase (ALK) positive large B-cell lymphoma, primary effusion lymphoma, and Burkitt lymphoma.
- Documented or suspected central nervous system (CNS) involvement by lymphoma.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 3, Open Label, Randomized Study Comparing the Efficacy and Safety of Odronextamab (REGN1979), an anti CD20 × anti-CD3 Bispecific Antibody, in Combination with CHOP (O-CHOP) versus Rituximab in Combination with CHOP (R-CHOP) in Previously Untreated Participants with Diffuse Large B-cell Lymphoma (DLBCL) (OLYMPIA-3).
- NCT06091865
Part 1 (safety run-in):
Primary objective:
To assess the safety, tolerability and dose limiting toxicities (DLTs) of odronextamab in combination with CHOP (O-CHOP) in participants previously untreated for Diffuse Large B-Cell Lymphoma (DLBCL) with high-risk features and determine the dose of odronextamab
to combine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in Part 2.
Secondary objectives:
a. To evaluate the preliminary anti-tumor activity of O-CHOP in participants with previously untreated DLBCL with high-risk features
b. To evaluate the pharmacokinetics (PK) of odronextamab when administered in combination with CHOP
c. To assess the immunogenicity of odronextamab when administered in combination with CHOP
Part 2 (randomized portion):
Primary objective: To compare the efficacy of O-CHOP with that of R-CHOP in participants with previously untreated DLBCL with an (International Prognostic Index) IPI score ≥3, and subsequently in all participants with an IPI score ≥2
Key secondary objective:
To compare therapeutic benefit with O-CHOP versus that with R-CHOP assessed by event-free survival (EFS), complete response (CR) and overall survival (OS)
Secondary objectives:
a. To compare supplemental measures of efficacy for O-CHOP versus R-CHOP
b. To compare safety and tolerability of O-CHOP with that of R-CHOP
c. To evaluate the PK of odronextamab when administered in combination with CHOP
d. To assess the immunogenicity of odronextamab
when administered in combination with CHOP
e. To compare measurable residual disease (MRD) with O-CHOP versus R-CHOP
f. To compare the treatment effects on patient reported physical function between O-CHOP and R-CHOP
g. To compare the treatment effects of O-CHOP versus R-CHOP on patient reported outcomes (PROs) including health-related quality of life, functioning and disease-related symptoms, as measured by EORTC QLQ-C30, FACT-LymS, EQ-5D-5L, two global anchors Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC), collected during study visits
h. To evaluate the overall impact of treatment toxicity based upon the single item GP5 of the validated FACT-G questionnaire ( I am bothered by side effects of treatment )
View All Details
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Protocol Number:
012307
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Principal Investigator:
Matthew Matasar
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Phase:
Phase III
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy multiple agents systemic
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Drugs Involved:
Odronextamab(REGN1979)
RITUXIMAB
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Read Inclusion & Exclusion Criteria
KEY Inclusion Criteria:
1. Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL, for whom next available standard of care therapy is not available or deemed ineligible according to the investigator (Part 1A only) 2. Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 4. Life expectancy ≥ 12 months 5. International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only; 6. Adequate hematologic and organ function, as defined in the protocol.
KEY Exclusion Criteria:
1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology 2. Another active malignancy, significant active disease or medical condition, as described in the protocol 3. Peripheral neuropathy Grade ≥3 4. Treatment with any systemic anti-lymphoma therapy, except for participants with relapsed/refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy. 5. Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment 6. Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol 7. Allergy/hypersensitivity to study drugs, as described in the protocol 8. Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol.Note: Other protocol-defined Inclusion/ Exclusion criteria apply
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.
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A Phase 3, Randomized, Open-Label Study Comparing the Efficacy and Safety of the Combination of Beleodaq-CHOP or Folotyn-COP to the CHOP Regimen Alone in Newly Diagnosed Patients with Peripheral T-Cell Lymphoma.
- NCT06072131
Part 1 (Dose Finding):
Primary Objective;
- To identify one of two dose-levels, each for belinostat and pralatrexate, that is optimal in polychemotherapy for the part 2 study based on safety and ORR at 3 months.
Part 2 (Efficacy and Safety):
Primary Objective:
- To compare the progression-free survival (PFS) of patients with newly diagnosed peripheral T-cell lymphoma (PTCL) treated for up to 6 cycles with belinostat in combination with CHOP (Bel-CHOP) or pralatrexate in combination with COP (Fol-COP) to CHOP alone.
Secondary Objectives:
- To compare the overall survival (OS) for patients with newly diagnosed PTCL treated with Bel-CHOP or Fol-COP to CHOP alone.
- To compare the objective response rate for patients with newly diagnosed PTCL treated with Bel-CHOP or Fol-COP to CHOP alone
- Treatment compliance
Exploratory Objectives
Dose intensity
To compare the duration of response for patients with newly diagnosed PTCL treated with Bel- CHOP or Fol-COP to CHOP alone
To compare the proportion of patients with newly diagnosed PTCL receiving hematopoietic stem cell transplantation who are treated with Bel-CHOP or Fol-COP to treatment with CHOP alone
Safety Objectives
To evaluate the safety profiles for patients with newly diagnosed PTCL treated with Bel-CHOP or Fol- COP compared to CHOP alone
View All Details
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Protocol Number:
012320
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Principal Investigator:
Yun Kyoung Tiger
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Phase:
Phase III
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Scope:
National
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Applicable Disease Sites:
Non-Hodgkin's Lymphoma
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Therapies Involved:
Chemotherapy multiple agents systemic
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Drugs Involved:
Belinostat
Pralatrexate (Folotyn)
-
Read Inclusion & Exclusion Criteria
Inclusion Criteria:
1. Patient with newly diagnosed, untreated histology-proven PTCL based on local pathology review who is eligible for receiving, Belinostat, Pralatrexate, and CHOP. Pathology material must be available at the site for each patient before enrollment so that it can be sent to the Sponsor (or designee) for later confirmation. The following subtypes, as defined by the updated World Health Organization (WHO) classification, may be included. This information should be available for eligibility: 1. Pathology subtype: - Peripheral T-cell lymphoma, not otherwise specified
- Angioimmunoblastic T-cell lymphoma
- Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) patients are eligible only if Brentuximab Vedotin (BV) is not commercially approved for use, not available in the country or patient is contraindicated to receive BV.
- Follicular T-cell lymphoma
- Others: Extra-nodal natural killer/T-cell lymphoma, nasal type; enteropathy-associated T-cell lymphoma; hepatosplenic T-cell lymphoma; and subcutaneous panniculitis-like T-cell lymphoma 2. CD30 expression and T-cell Follicular Helper (TFH) phenotype status must be available for documentation. 2. Patient has at least 1 site of measurable disease according to Response Evaluation Criteria in Lymphoma (RECIL) 2017 criteria as assessed by the local Investigator (Appendix 3) 3. Patient has an Eastern Cooperative Oncology Group performance (ECOG) status ≤2 4. For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by: 1. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement 2. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement 3. Total bilirubin ≤1.5 mg/dL 4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) 5. Calculated creatinine clearance of ≥ 60 mL/min 5. Part 2 (Efficacy and Safety) - disease related hypoplasia, hepatological or renal dysfunction can be included if any of the treatment groups can be administered based on package insert recommendation with the following restrictions: 1. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement 2. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement 3. Total bilirubin ≤1.5 mg/dL 4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) 5. Calculated creatinine clearance of ≥ 60 mL/min 6. UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal) and must be available for documentation. 7. Patient must be willing and capable of giving written informed consent and must be able to adhere to dosing and visit schedules and meet all study requirements 8. Patient (male or female) is at least 18 years of age at the time of informed consent 9. Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 6 months after the last dose of study treatment. 10. Females of childbearing potential must have a negative urine pregnancy test within 4 weeks prior to the first day of study treatment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test.
Exclusion Criteria:
A patient will not be eligible for inclusion if ANY of the criteria listed below apply: 1. Patients with a diagnosis of: 1. Precursor T-cell lymphoma or leukemia 2. Adult T-cell lymphoma/leukemia 3. T-cell prolymphocytic leukemia 4. T-cell large granular lymphocytic leukemia 5. Primary cutaneous type ALCL 6. Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) 7. ALCL if they can be treated with Brentuximab Vedotin (BV) 2. Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week before randomization; drug can be resumed if the treatment doesn't include belinostat 3. Patient with an active concurrent malignancy/life-threatening disease with the exception of non melanoma skin tumors and in situ cervical cancer if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. If there is a history of prior malignancies/life-threatening diseases, the patient must be disease free for at least 5 years 4. Prior histone deacetylase (HDAC) inhibitor or pralatrexate therapy 5. Any known cardiac abnormalities such as baseline prolongation of QT/corrected QT (QTc) interval (i.e. demonstration of a QTc interval >450 msec); long QT syndrome; myocardial infarction within 6 months prior to starting study; history of significant cardiovascular disease; the required use of a concomitant medication that may cause Torsades de Pointes 6. Patient with uncontrolled hypertension 7. Patients status on the following: 1. Has a known HIV-positive diagnosis with uncontrolled and detectable viral load 2. Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and detectable viral load or immunological evidence of chronic active disease 8. Patient with central nervous system metastasis 9. Patient with an active uncontrolled infection, underlying medical condition, laboratory abnormality, or other serious illness that would impair the ability of the patient to receive protocol treatment 10. Patient who has used any investigational drugs, biologics, or devices within 28 days prior to study treatment or plans to use any of these during the course of the study 11. Patient with a known history of drug or alcohol abuse 12. Pregnant or breastfeeding women
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.