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
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03575351 Recruiting July 2, 2018 August 31, 2020

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.

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

N/A


study design
Study Type: Interventional
Estimated Enrollment : 182 participants
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 2018
Estimated Primary Completion Date: January 2024
Estimated Study Completion Date: January 2024

Arms and interventions
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
JCAR017
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), 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: 1. Complete response rate (CRR) [ Time Frame: Approximately 3 years ]
Percentage of subjects achieving a complete response (CR)
2. Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
Time from randomization to PD 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 due to efficacy concerns 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 using 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, fatigue, physical and cognitive functions.
9. 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.
10. Reasons for hospital resource utilization [ Time Frame: Approximately 3 years ]
Will be assessed based on reasons for hospitalization
11. Rate of hematopoietic stem cell transplant (HSCT) [ Time Frame: Approximately 3 years ]
Rate of completion of HDCT and HSCT
12. 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
13. 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

Eligibility Criteria
Ages Eligible for Study: 18 to 75 Years (Adult, Older Adult)
Sexes Eligible for Study: All
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 ≤ 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.


Contacts and Locations
Contacts

Contact:

Locations
United States, Arizona Virginia G Piper Cancer Center Scottsdale
United States, Arizona Mayo Clinic Arizona Scottsdale
United States, California University of California San Francisco San Francisco
United States, Colorado University of Colorado Cancer Center Aurora
United States, Florida Mayo Clinic - Jacksonville Jacksonville
United States, Florida H. Lee Moffitt Cancer Center and Research Institute Tampa
United States, Georgia Emory University Atlanta
United States, Georgia Blood and Marrow Transplant Group of Georgia Atlanta
United States, Illinois Northwestern University-Feinberg School of Medicine Chicago
United States, Illinois Loyola University Medical Center Cardinal Bernardin Cancer Center Maywood
United States, Massachusetts Massachusetts General Hospital / Dana-Farber Cancer Institute Boston
United States, Massachusetts Beth Israel Deaconess Medical Center Boston
United States, Michigan University of Michigan Ann Arbor
United States, Michigan Barbara Ann Karmanos Cancer Center Detroit
United States, Minnesota University of Minnesota Minneapolis
United States, Minnesota Mayo Clinic - Rochester Rochester
United States, Nebraska University of Nebraska Medical Center Omaha
United States, New Jersey John Theurer Cancer Center at Hackensack University Medical Center Hackensack
United States, New York Roswell Park Cancer Institute Buffalo
United States, New York Memorial Sloan Kettering Cancer Center New York
United States, North Carolina Levine Cancer Institute Charlotte
United States, Oklahoma University of Oklahoma Peggy and Charles Stephenson Cancer Center Oklahoma City
United States, Oregon Oregon Health and Science University Portland
United States, Pennsylvania Hillman Cancer Institute at UPMC Pittsburgh
United States, Texas Baylor University Medical Center Dallas
United States, Texas The University of Texas - MD Anderson Cancer Center Houston
United States, Virginia Virginia Commonwealth University Richmond
United States, Washington Fred Hutchinson Cancer Research Center Seattle
Belgium UZ Gent Gent
France CHRU-Hopital Claude Huriez Lille
France Institut Paoli Calmette Hematologie Marseille cedex
France Centre Hospitalier Lyon Sud Pierre Benite
France Gustave Roussy Villejuif CEDEX
Germany Robert-Rössle-Klinik im HELIOS Klinikum Berlin-Buch Klinik für Hämatologie, Onkologie u. Tumorimmuno Berlin
Germany Universitaetsklinikum Carl Gustav Carus Dresden
Germany Universitaetsklinik Hamburg - Eppendorf Hamburg
Germany Universitat zu Koln Köln
Germany Universitatsklinik Muenster Muenster
Germany LMU Klinikum der Universitat München
Italy La Sapienza, University of Rome Rome
Italy Istituto Clinico Humanitas Rozzano (MI)
Italy Azienda Ospedaliera Citta della Salute e della Scienza di Torino Torino
Japan Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Bunkyo-ku
Japan National Cancer Center Hospital Chuo-ku
Japan Toranomon Hospital Minato-ku
Japan Osaka City University Hospital Osaka
Netherlands Erasmus Medical Center-Daniel den Hoed Rotterdam
Spain Hospital Clinic i Provincial de Barcelona - ICMHO Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
Sweden Karolinska Universitetssjukhuset - Huddinge Stockholm
Switzerland Universitatsspital Bern Bern
United Kingdom UCL Cancer Institute London
United Kingdom University Hospital Southampton NHS Foundation Trust - Southampton General Hospital Southampton
Sponsors and Collaborators
Celgene
Investigator
Study Director : Alessandro Crotta, MD Celgene
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT03575351     
Other Study ID Numbers : JCAR017-BCM-003, U1111-1213-1944, 2018-000929-32
First Posted : July 2, 2018
Last Update Posted : August 31, 2020
Last Verified : August 2020
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: Safety
JCAR017
Liso-cel
Relapsed
Non-Hodgkin Lymphomas
DLBCL
Efficacy
High-Risk
Refractory
B-cell NHL
Additional relevant MeSH terms :
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell