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Trial record 1 of 1 for:    NCT03575351
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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)

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ClinicalTrials.gov Identifier: NCT03575351
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE June 14, 2018
First Posted Date  ICMJE July 2, 2018
Last Update Posted Date August 20, 2019
Actual Study Start Date  ICMJE November 5, 2018
Estimated Primary Completion Date May 20, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
Event-free survival (EFS) [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
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
Change History Complete list of historical versions of study NCT03575351 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • Complete response rate (CRR) [ Time Frame: Approximately 3 years ]
    Percentage of subjects achieving a complete response (CR)
  • Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
    Time from randomization to PD or death from any cause, whichever occurs first
  • Overall survival (OS) [ Time Frame: Approximately 4.5 years ]
    Time from randomization to time of death due to any cause
  • 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
  • Duration of response (DOR) [ Time Frame: Approximately 3 years ]
    Time from first response to disease progression, start of new antineoplastic therapy due to efficacy concerns or death from any cause
  • 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.
  • 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)
  • 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.
  • 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.
  • 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.
  • Reasons for hospital resource utilization [ Time Frame: Approximately 3 years ]
    Will be assessed based on reasons for hospitalization
  • Rate of hematopoietic stem cell transplant (HSCT) [ Time Frame: Approximately 3 years ]
    Rate of completion of HDCT and HSCT
  • 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
  • Hospital resource utilization (HRU) [ 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 and reasons for hospitalization
Original Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
  • 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
  • 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
  • Overall survival (OS) [ Time Frame: Approximately 4.5 years ]
    Time from randomization to time of death due to any cause
  • 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
  • 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
  • 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.
  • 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)
  • 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.
  • 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.
  • 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.
  • Reasons for hospital resource utilization [ Time Frame: Approximately 3 years ]
    Will be assessed based on reasons for hospitalization
  • Rate of hematopoietic stem cell transplant (HSCT) [ Time Frame: Approximately 3 years ]
    Rate of completion of HDCT and HSCT
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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).
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Non-Hodgkin
Intervention  ICMJE
  • Drug: Standard of Care
    Standard of Care
  • Genetic: JCAR017
    JCAR017
    Other Name: lisocabtagene maraleucel or liso-cel
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 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.
    Intervention: Genetic: JCAR017
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 28, 2018)
182
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 20, 2023
Estimated Primary Completion Date May 20, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  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 of the elderly and Burkitt lymphoma.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Italy,   Japan,   Netherlands,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03575351
Other Study ID Numbers  ICMJE JCAR017-BCM-003
U1111-1213-1944 ( Registry Identifier: WHO )
2018-000929-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alessandro Crotta, MD Celgene
PRS Account Celgene
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP