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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 (TRANSFORM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03575351
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : December 27, 2018
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: Standard of Care Genetic: JCAR017 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : October 14, 2022
Estimated Study Completion Date : January 13, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Active Comparator: 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.
Drug: Standard of Care
Standard of Care

Experimental: 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.
Genetic: JCAR017
Other Name: lisocabtagene maraleucel or liso-cel

Primary Outcome Measures :
  1. Event-free survival (EFS) [ Time Frame: Approximately 3 years ]
    Time from randomization to death from any cause, progressive disease (PD), as assessed by the independent review committee (IRC) or start of new antineoplastic therapy, whichever occurs first

Secondary Outcome Measures :
  1. Complete response rate (CRR) [ Time Frame: Approximately 3 years ]
    Percentage of subjects achieving a complete response (CR) according to the Lugano Classification assessed by the IRC

  2. Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
    Time from randomization to PD, SD at 1st response assessment as per protocol schedule, as per IRC review or death from any cause, whichever occurs first

  3. Overall survival (OS) [ Time Frame: Approximately 4.5 years ]
    Time from randomization to time of death due to any cause

  4. Overall response rate (ORR) [ Time Frame: 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

  5. Duration of response (DOR) [ Time Frame: Approximately 3 years ]
    Time from first response to disease progression, start of new antineoplastic therapy or death from any cause

  6. PFS on next line of treatment (PFS-2) [ Time Frame: Approximately 3 years ]
    Time from randomization to second objective disease progression or death from any cause, whichever is first.

  7. Adverse Events (AEs) [ Time Frame: 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)

  8. HRQoL parameters assessed by European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30) [ Time Frame: 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.

  9. HRQoL parameters assessed by EQ-5D-5L [ Time Frame: Approximately 3 years ]
    European Quality of Life-5 Dimensions health state classifier to 5 Levels questionnaire: EQ-5D is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal.

  10. HRQoL parameters assessed by FACT-Lym "Additional concerns" subscale [ Time Frame: 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.

  11. Reasons for hospital resource utilization [ Time Frame: Approximately 3 years ]
    Will be assessed based on reasons for hospitalization

  12. Rate of hematopoietic stem cell transplant (HSCT) [ Time Frame: Approximately 3 years ]
    Rate of completion of HDCT and HSCT

  13. Frequency of hospital resource utilization [ Time Frame: Approximately 3 years ]
    Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
  2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed FL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology.
  4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
  5. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening.
  6. Adequate organ function
  7. Participants must agree to use effective contraception

Exclusion Criteria:

  1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
  2. Subjects planned to undergo allogeneic stem cell transplantation.
  3. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV (Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma, transformed indolent NHL except transformed FL.
  4. 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
  5. Treatment with any prior gene therapy product.
  6. Subjects who have received previous CD19-targeted therapy.
  7. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
  9. Active autoimmune disease requiring immunosuppressive therapy.
  10. 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.
  11. History or presence of clinically relevant central nervous system (CNS) pathology
  12. Pregnant or nursing (lactating) women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03575351

Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599

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Sponsors and Collaborators
Study Director: Alessandro Crotta, MD Celgene

Responsible Party: Celgene Identifier: NCT03575351     History of Changes
Other Study ID Numbers: JCAR017-BCM-003
U1111-1213-1944 ( Registry Identifier: WHO )
2018-000929-32 ( EudraCT Number )
First Posted: July 2, 2018    Key Record Dates
Last Update Posted: December 27, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Non-Hodgkin Lymphomas

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases