A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Drug: Standard of CareGenetic: JCAR017
- Registration Number
- NCT03575351
- Lead Sponsor
- Celgene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 184
- 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 ≤ 1.
- 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
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Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
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Subjects planned to undergo allogeneic stem cell transplantation.
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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).
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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
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Treatment with any prior gene therapy product.
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Subjects who have received previous CD19-targeted therapy.
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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.
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Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
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Active autoimmune disease requiring immunosuppressive therapy.
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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.
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History or presence of clinically relevant central nervous system (CNS) pathology
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Pregnant or nursing (lactating) women.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A - Standard of Care (SOC) Standard of Care 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. Arm B - JCAR017 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.
- Primary Outcome Measures
Name Time Method Event-free survival (EFS) Approximately 3 years Time from randomization to death from any cause, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR), or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first
- Secondary Outcome Measures
Name Time Method Rate of hematopoietic stem cell transplant (HSCT) Approximately 3 years Rate of completion of HDCT and HSCT
Frequency of hospital resource utilization Approximately 3 years Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days
PFS on next line of treatment (PFS-2) Approximately 3 years Time from randomization to second objective disease progression or death from any cause, whichever is first.
Reasons for hospital resource utilization Approximately 3 years Will be assessed based on reasons for hospitalization
Complete response rate (CRR) Approximately 3 years Percentage of subjects achieving a complete response (CR)
HRQoL using European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30) Approximately 3 years European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire: The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of life, fatigue, physical and cognitive functions.
HRQoL parameters assessed by FACT-Lym "Additional concerns" subscale Approximately 3 years Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale: Only the LYM subscale will be administered in this study. This scale addresses symptoms and functional limitations (15 item) that are important to lymphoma patients.
Hospital resource utilization (HRU) Approximately 3 years Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days and reasons for hospitalization
Progression-free survival (PFS) Approximately 3 years Time from randomization to PD or death from any cause, whichever occurs first
Overall survival (OS) Approximately 4.5 years Time from randomization to time of death due to any cause
Overall response rate (ORR) Approximately 3 years Percentage of subjects achieving an objective response of partial response (PR) or better according to the Lugano Classification as assessed by IRC review
Duration of response (DOR) Approximately 3 years Time from first response to disease progression, start of new antineoplastic therapy due to efficacy concerns or death from any cause
Adverse Events (AEs) Approximately 3 years Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)
Trial Locations
- Locations (54)
Loyola University Medical Center Cardinal Bernardin Cancer Center
🇺🇸Maywood, Illinois, United States
Local Institution - 109
🇺🇸Dallas, Texas, United States
Local Institution - 350
🇧🇪Gent, Belgium
Local Institution - UNK 25
🇫🇮Helsinki, Finland
Local Institution - 122
🇺🇸Chicago, Illinois, United States
Local Institution - 104
🇺🇸Boston, Massachusetts, United States
Local Institution - 123
🇺🇸Pittsburgh, Pennsylvania, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Local Institution - 108
🇺🇸Atlanta, Georgia, United States
Local Institution - 102
🇺🇸Boston, Massachusetts, United States
Local Institution - 111
🇺🇸Buffalo, New York, United States
Local Institution - 125
🇺🇸Charlotte, North Carolina, United States
Local Institution - 124
🇺🇸Houston, Texas, United States
Local Institution - 114
🇺🇸Richmond, Virginia, United States
Local Institution - 403
🇫🇷Pierre Benite, France
Local Institution - 451
🇩🇪Berlin, Germany
Local Institution - 200
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 203
🇯🇵Osaka, Osaka-shi, Japan
Local Institution - 550
🇳🇱Rotterdam, Netherlands
Local Institution - 700
🇨🇭Bern, Switzerland
Local Institution - 600
🇪🇸Barcelona, Spain
Local Institution - 601
🇪🇸Madrid, Spain
Local Institution - 452
🇩🇪Hamburg, Germany
Local Institution - 453
🇩🇪München, Germany
Local Institution - 502
🇮🇹Torino, Italy
Local Institution - 107
🇺🇸Atlanta, Georgia, United States
Local Institution - 129
🇺🇸Scottsdale, Arizona, United States
Local Institution - 116
🇺🇸Scottsdale, Arizona, United States
Local Institution - 121
🇺🇸Hackensack, New Jersey, United States
Local Institution - 117
🇺🇸New York, New York, United States
Local Institution - 110
🇺🇸Seattle, Washington, United States
Local Institution - 401
🇫🇷Lille, France
Local Institution - 400
🇫🇷Marseille cedex, France
Local Institution - 402
🇫🇷Villejuif CEDEX, France
Local Institution - 455
🇩🇪Dresden, Saxony, Germany
Local Institution - 454
🇩🇪Muenster, Germany
Local Institution - 450
🇩🇪Köln, Germany
Local Institution - 501
🇮🇹Rozzano (MI), Italy
Local Institution - 500
🇮🇹Rome, Italy
Local Institution - 201
🇯🇵Minato-ku, Tokyo, Japan
Local Institution - 202
🇯🇵Bunkyo-ku, Japan
Local Institution - 650
🇸🇪Stockholm, Sweden
Local Institution - 750
🇬🇧London, United Kingdom
Local Institution - 112
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 101
🇺🇸Portland, Oregon, United States
Local Institution - 115
🇺🇸San Francisco, California, United States
Local Institution - 119
🇺🇸Detroit, Michigan, United States
Local Institution - 106
🇺🇸Aurora, Colorado, United States
Local Institution - 126
🇺🇸Tampa, Florida, United States
Local Institution - 120
🇺🇸Ann Arbor, Michigan, United States
Local Institution - 103
🇺🇸Rochester, Minnesota, United States
Local Institution - 100
🇺🇸Omaha, Nebraska, United States
Local Institution - 127
🇺🇸Oklahoma City, Oklahoma, United States
Local Institution - 751
🇬🇧Southampton, Hampshire, United Kingdom