Clinical Trials /

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

NCT03575351

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • Grade 3b Follicular Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT03575351

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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).

Clinical Trial IDs

  • ORG STUDY ID: JCAR017-BCM-003
  • SECONDARY ID: U1111-1213-1944
  • SECONDARY ID: 2018-000929-32
  • NCT ID: NCT03575351

Conditions

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
Standard of CareArm A - Standard of Care (SOC)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A - Standard of Care (SOC)Active ComparatorSubjects 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.
  • Standard of Care
Arm B - JCAR017ExperimentalLymphodepleting 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.

    Eligibility Criteria

            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 ≤ 1.

          3. 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.

          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. (Deauville score 4 or 5)

          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, 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).

          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. 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.

          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.
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Event-free survival (EFS)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description: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

    Measure:Complete response rate (CRR)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Percentage of subjects achieving a complete response (CR)
    Measure:Progression-free survival (PFS)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Time from randomization to PD or death from any cause, whichever occurs first
    Measure:Overall survival (OS)
    Time Frame:Approximately 4.5 years
    Safety Issue:
    Description:Time from randomization to time of death due to any cause
    Measure:Overall response rate (ORR)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Percentage of subjects achieving an objective response of partial response (PR) or better according to the Lugano Classification as assessed by IRC review
    Measure:Duration of response (DOR)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Time from first response to disease progression, start of new antineoplastic therapy due to efficacy concerns or death from any cause
    Measure:PFS on next line of treatment (PFS-2)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Time from randomization to second objective disease progression or death from any cause, whichever is first.
    Measure:Adverse Events (AEs)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups)
    Measure:HRQoL using European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description: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.
    Measure:HRQoL parameters assessed by FACT-Lym "Additional concerns" subscale
    Time Frame:Approximately 3 years
    Safety Issue:
    Description: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.
    Measure:Reasons for hospital resource utilization
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Will be assessed based on reasons for hospitalization
    Measure:Rate of hematopoietic stem cell transplant (HSCT)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Rate of completion of HDCT and HSCT
    Measure:Frequency of hospital resource utilization
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days
    Measure:Hospital resource utilization (HRU)
    Time Frame:Approximately 3 years
    Safety Issue:
    Description:Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days and reasons for hospitalization

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Celgene

    Trial Keywords

    • Non-Hodgkin Lymphomas
    • DLBCL
    • Efficacy
    • Safety
    • JCAR017
    • Liso-cel
    • High-Risk
    • Relapsed
    • Refractory
    • B-cell NHL

    Last Updated

    June 10, 2021