A Global Randomized Multicenter Phase 3 Trial of JCAR017 Compared to Standard of Care in Adult Subjects With High-risk, Second-line, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 184
- 试验地点
- 54
- 主要终点
- Event-free Survival (EFS) Per Independent Review Committee (IRC)
研究概览
简要总结
The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.
This is a randomized, open-label, parallel-group, multi-center trial in adult subjects with Relapsed or refractory (R/R) aggressive Non-Hodgkin lymphoma (NHL) to compare safety and efficacy between the standard of care (SOC) strategy versus JCAR017 (also known as lisocabtagene maraleucel or liso-cel). Subjects will be randomized to either receive SOC (Arm A) or to receive JCAR017 (Arm B).
All subjects randomized to Arm A will receive Standard of care (SOC) salvage therapy (R-DHAP, RICE or R-GDP) as per physician's choice before proceeding to High dose chemotherapy (HDCT) and Hematopoietic stem cell transplant (HSCT).
Subjects from Arm A may be allowed to cross over and receive JCAR017 upon confirmation of an EFS event.
Subjects randomized to Arm B will receive Lymphodepleting (LD) chemotherapy followed by JCAR017 infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]), primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large B-cell lymphoma (THRBCL) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology.
- •Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
- •[18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
- •Adequate organ function
- •Participants must agree to use effective contraception
排除标准
- •Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
- •Subjects planned to undergo allogeneic stem cell transplantation.
- •Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL, Burkitt lymphoma or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter transformation).
- •Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following noninvasive malignancies:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
- •Other completely resected stage 1 solid tumor with low risk for recurrence
- •Treatment with any prior gene therapy product.
- •Subjects who have received previous CD19-targeted therapy.
- •Subjects with active hepatitis B, or active hepatitis C are excluded. Subjects with negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy. Subjects with a history of or active human immunodeficiency virus (HIV) are excluded.
- •Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
- •Active autoimmune disease requiring immunosuppressive therapy.
- •History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
- •History or presence of clinically relevant central nervous system (CNS) pathology
- •Pregnant or nursing (lactating) women.
研究组 & 干预措施
Arm A - Standard of Care (SOC)
Subjects should receive SOC (R-DHAP, R-ICE or R-GDP) followed by HDCT (BEAM) and HSCT. Standard of care regimen will be administered as per investigator decision.
干预措施: Standard of Care (Drug)
Arm B - JCAR017
Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently followed by JCAR017 infusion.
干预措施: JCAR017 (Genetic)
结局指标
主要结局
Event-free Survival (EFS) Per Independent Review Committee (IRC)
时间窗: From randomization to death from any cause, PD, failure to achieve CR or PR by 9 weeks post randomization, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first (Up to 36 months)
Time from randomization to death, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR) by 9 weeks or start of new antineoplastic therapy, whichever occurs first. CR: Target nodes masses must regress to ≤ 1.5cm in LDi, no extralymphatic sites, no new lesions. PR: ≥ 50% decrease in sum of diameters of up to 6 target nodes and extranodal sites, no new lesions, spleen must have regressed \> 50% in length. PD: LDi \> 1.5cm, increase by ≥ 50% from PPD nadir, an increase in LDi or SDi from nadir, 0.5 cm for lesions ≤ 2cm, 1.0cm for lesions \> 2cm. Complete metabolic response: Lymph nodes score 1, 2, 3 with/without residual mass on 5-point scale, no new lesions, no FDG-avid disease. Partial metabolic response: Lymph nodes score 4 or 5, reduced uptake from baseline, no new lesions, residual uptake higher than normal, reduced from baseline. Progressive metabolic disease: Score 4 or 5 with an increase in uptake intensity from baseline and/or new FDG-avid.
次要结局
- Overall Survival (OS)(From randomization to time of death due to any cause (Up to 36 months))
- Complete Response Rate (CRR)(From randomization up to 3 years post randomization (Up to 36 months))
- Number of Participants With Complete Response (CR)(From randomization up to 3 years post randomization (Up to 36 months))
- Overall Response Rate (ORR)(From randomization to PR or CR (Up to 36 months))
- Progression-free Survival (PFS)(From randomization to progression, or death from any cause, whichever occurs first (Up to 36 months))
- Progression-free Survival (PFS) Rate(Months 6, 12, 18, 24, 36)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From randomization to 90 days after last dose or start of new antineoplastic therapy, whichever occurs first (Up to 16.5 months))
- Duration of Response (DoR) Per Independent Review Committee (IRC)(From randomization to to disease progression, start of new antineoplastic therapy due to efficacy concerns or death, whichever occurs first (Up to 36 months))
- Overall Survival (OS) Rate(Months 6, 12, 18, 24, 36)
- Number of Participants With Progression-free Survival on Next Line of Treatment (PFS-2)(From randomization to second objective progression, or death from any cause, whichever occurs first (Up to 36 months))
- Change From Baseline in Selected Chemistry Parameters 1(baseline, months 1, 2, 3, 4, 6, 9, 12, 18, 24, 36)
- Event-free Survival (EFS) Rate(Months 6, 12, 18, 24, 36)
- Overall Response Rate (ORR) by Subgroups(From randomization to PR or CR (Up to 36 months))
- Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs)(From randomization to 90 days after last dose or start of new antineoplastic therapy, whichever occurs first (Up to 16.5 months))
- Change From Baseline in Hematology Parameters 1: Hemoglobin(baseline, months 1, 2, 3, 4, 6, 9, 12, 18, 24, 36)
- Change From Baseline in Selected Hematology Parameters 2(baseline, months 1, 2, 3, 4, 6, 9, 12, 18, 24, 36)
- Progression-free Survival (PFS) by Subgroups(From randomization to progression, or death from any cause, whichever occurs first (Up to 36 months))
- Overall Survival (OS) by Subgroups(From randomization to time of death due to any cause (Up to 36 months))
- Hospital Resource Utilization (HRU) Results(Up to 36 months)
- Change From Baseline in Selected Chemistry Parameters 2(baseline, months 1, 2, 3, 4, 6, 9, 12, 18, 24, 36)
- Event-free Survival (EFS) by Subgroups(From randomization to death from any cause, PD, failure to achieve CR or PR by 9 weeks post randomization, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first (Up to 36 months))
- Change From Baseline in the European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30)(baseline, months 1, 6, 9, 12, 18, 24, 36)
- Change From Baseline in the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-Lym)(baseline, months 1, 6, 9, 12, 18, 24, 36)
- Percentage of Participants Completing High Dose Chemotherapy (HDCT)(Up to 5 months after first dose)
- Percentage of Participants Completing Hematopoietic Stem Cell Transplant (HSCT)(Up to 5 months after first dose)