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History of Changes for Study: NCT03575351
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)
Latest version (submitted November 11, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 28, 2018 None (earliest Version on record)
2 September 28, 2018 Recruitment Status, Study Status, Contacts/Locations, Oversight and Study Identification
3 October 16, 2018 Contacts/Locations and Study Status
4 October 22, 2018 Study Status
5 November 1, 2018 Study Status
6 November 30, 2018 Contacts/Locations and Study Status
7 December 10, 2018 Contacts/Locations and Study Status
8 December 19, 2018 Contacts/Locations and Study Status
9 December 25, 2018 Contacts/Locations and Study Status
10 January 17, 2019 Study Status and Contacts/Locations
11 January 24, 2019 Study Status
12 February 28, 2019 Study Status, Outcome Measures, Contacts/Locations, Eligibility and Conditions
13 May 13, 2019 Contacts/Locations and Study Status
14 May 22, 2019 Contacts/Locations and Study Status
15 June 6, 2019 Study Status and Contacts/Locations
16 June 18, 2019 Contacts/Locations and Study Status
17 July 22, 2019 Contacts/Locations and Study Status
18 August 19, 2019 Contacts/Locations and Study Status
19 October 16, 2019 Contacts/Locations and Study Status
20 December 19, 2019 Study Status and Contacts/Locations
21 January 13, 2020 Outcome Measures, Study Status, Contacts/Locations and Eligibility
22 January 29, 2020 Study Status and Contacts/Locations
23 February 25, 2020 Study Status and Contacts/Locations
24 April 7, 2020 Study Status and Contacts/Locations
25 July 16, 2020 Study Status and Contacts/Locations
26 August 3, 2020 Study Status and Contacts/Locations
27 August 9, 2020 Study Status
28 August 19, 2020 Study Status
29 August 28, 2020 Contacts/Locations and Study Status
30 January 6, 2021 Study Status and Contacts/Locations
31 June 9, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
32 March 12, 2022 Contacts/Locations, Study Status and Study Design
33 June 10, 2022 Study Status and Contacts/Locations
34 July 18, 2022 Study Status and Contacts/Locations
35 July 21, 2022 References, Contacts/Locations and Study Status
36 July 28, 2022 Contacts/Locations and Study Status
37 August 1, 2022 Study Status and Contacts/Locations
38 August 19, 2022 Contacts/Locations and Study Status
39 September 1, 2022 Study Status and Contacts/Locations
40 October 4, 2022 Study Status and Contacts/Locations
41 November 4, 2022 Study Status and Contacts/Locations
42 November 9, 2022 Contacts/Locations and Study Status
43 November 11, 2022 Contacts/Locations and Study Status
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Study NCT03575351
Submitted Date:  June 28, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: JCAR017-BCM-003
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 (TRANSFORM)
Official Title: A Global Randomized Multicenter Phase 3 Trial 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).
Secondary IDs: U1111-1213-1944 [Registry Identifier: WHO]
2018-000929-32 [EudraCT Number]
Open or close this module Study Status
Record Verification: June 2018
Overall Status: Not yet recruiting
Study Start: July 16, 2018
Primary Completion: November 14, 2022 [Anticipated]
Study Completion: November 14, 2022 [Anticipated]
First Submitted: June 14, 2018
First Submitted that
Met QC Criteria:
June 28, 2018
First Posted: July 2, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
June 28, 2018
Last Update Posted: July 2, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Celgene
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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:
Open or close this module Conditions
Conditions: Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkin Lymphomas
DLBCL
Efficacy
Safety
JCAR017
Liso-cel
High-Risk
Relapsed
Refractory
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 182 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
JCAR017
Other Names:
  • lisocabtagene maraleucel or liso-cel
Open or close this module Outcome Measures
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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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 ≤ 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.
Open or close this module Contacts/Locations
Central Contact Person: Associate Director Clinical Trial Disclosure
Telephone: 1-888-260-1599
Email: clinicaltrialdisclosure@celgene.com
Study Officials: Alessandro Crotta, MD
Study Director
Celgene
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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