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

Lymphoma, Non-Hodgkin Clinical Trial

— TRANSFORM  

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 Details — Status: Completed

Administrative data

• NCT number: NCT03575351
• Other study ID #: JCAR017-BCM-003
• Secondary ID: U1111-1213-19442
• Status: Completed
• Phase: Phase 3
• Start date: October 23, 2018
• Est. completion date: October 23, 2023

Study information

• Verified date: November 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: October 23, 2023
• Est. primary completion date: October 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Standard of Care
Standard of Care

Genetic:
• JCAR017
JCAR017

Locations

Country	Name	City	State
Belgium	Local Institution - 350	Gent
Finland	Local Institution - UNK 25	Helsinki
France	Local Institution - 401	Lille
France	Local Institution - 400	Marseille cedex
France	Local Institution - 403	Pierre Benite
France	Local Institution - 402	Villejuif CEDEX
Germany	Local Institution - 451	Berlin
Germany	Local Institution - 455	Dresden	Saxony
Germany	Local Institution - 452	Hamburg
Germany	Local Institution - 450	Köln
Germany	Local Institution - 454	Muenster
Germany	Local Institution - 453	München
Italy	Local Institution - 500	Rome
Italy	Local Institution - 501	Rozzano (MI)
Italy	Local Institution - 502	Torino
Japan	Local Institution - 202	Bunkyo-ku
Japan	Local Institution - 200	Chuo-ku	Tokyo
Japan	Local Institution - 201	Minato-ku	Tokyo
Japan	Local Institution - 203	Osaka	Osaka-shi
Netherlands	Local Institution - 550	Rotterdam
Spain	Local Institution - 600	Barcelona
Spain	Local Institution - 601	Madrid
Sweden	Local Institution - 650	Stockholm
Switzerland	Local Institution - 700	Bern
United Kingdom	Local Institution - 750	London
United Kingdom	Local Institution - 751	Southampton	Hampshire
United States	Local Institution - 120	Ann Arbor	Michigan
United States	Local Institution - 107	Atlanta	Georgia
United States	Local Institution - 108	Atlanta	Georgia
United States	Local Institution - 106	Aurora	Colorado
United States	Local Institution - 102	Boston	Massachusetts
United States	Local Institution - 104	Boston	Massachusetts
United States	Local Institution - 111	Buffalo	New York
United States	Local Institution - 125	Charlotte	North Carolina
United States	Local Institution - 122	Chicago	Illinois
United States	Local Institution - 109	Dallas	Texas
United States	Local Institution - 119	Detroit	Michigan
United States	Local Institution - 121	Hackensack	New Jersey
United States	Local Institution - 124	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Loyola University Medical Center Cardinal Bernardin Cancer Center	Maywood	Illinois
United States	Local Institution - 112	Minneapolis	Minnesota
United States	Local Institution - 117	New York	New York
United States	Local Institution - 127	Oklahoma City	Oklahoma
United States	Local Institution - 100	Omaha	Nebraska
United States	Local Institution - 123	Pittsburgh	Pennsylvania
United States	Local Institution - 101	Portland	Oregon
United States	Local Institution - 114	Richmond	Virginia
United States	Local Institution - 103	Rochester	Minnesota
United States	Local Institution - 115	San Francisco	California
United States	Local Institution - 116	Scottsdale	Arizona
United States	Local Institution - 129	Scottsdale	Arizona
United States	Local Institution - 110	Seattle	Washington
United States	Local Institution - 126	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Belgium,  Finland,  France,  Germany,  Italy,  Japan,  Netherlands,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting