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

NCT ID: NCT03575351

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-23
• Study Completion Date: 2023-10-23

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.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

Standard of Care

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.

Group Type: EXPERIMENTAL

JCAR017

Intervention Type: GENETIC

JCAR017

Interventions

Standard of Care

Standard of Care

Intervention Type: DRUG

JCAR017

JCAR017

Intervention Type: GENETIC

Other Intervention Names

lisocabtagene maraleucel or liso-cel

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 129

Scottsdale, Arizona, United States

Local Institution - 116

Scottsdale, Arizona, United States

Local Institution - 115

San Francisco, California, United States

Local Institution - 106

Aurora, Colorado, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Local Institution - 126

Tampa, Florida, United States

Local Institution - 108

Atlanta, Georgia, United States

Local Institution - 107

Atlanta, Georgia, United States

Local Institution - 122

Chicago, Illinois, United States

Loyola University Medical Center Cardinal Bernardin Cancer Center

Maywood, Illinois, United States

Local Institution - 102

Boston, Massachusetts, United States

Local Institution - 104

Boston, Massachusetts, United States

Local Institution - 120

Ann Arbor, Michigan, United States

Local Institution - 119

Detroit, Michigan, United States

Local Institution - 112

Minneapolis, Minnesota, United States

Local Institution - 103

Rochester, Minnesota, United States

Local Institution - 100

Omaha, Nebraska, United States

Local Institution - 121

Hackensack, New Jersey, United States

Local Institution - 111

Buffalo, New York, United States

Local Institution - 117

New York, New York, United States

Local Institution - 125

Charlotte, North Carolina, United States

Local Institution - 127

Oklahoma City, Oklahoma, United States

Local Institution - 101

Portland, Oregon, United States

Local Institution - 123

Pittsburgh, Pennsylvania, United States

Local Institution - 109

Dallas, Texas, United States

Local Institution - 124

Houston, Texas, United States

Local Institution - 114

Richmond, Virginia, United States

Local Institution - 110

Seattle, Washington, United States

Local Institution - 350

Ghent, , Belgium

Local Institution - UNK 25

Helsinki, , Finland

Local Institution - 401

Lille, , France

Local Institution - 400

Marseille, , France

Local Institution - 403

Pierre-Bénite, , France

Local Institution - 402

Villejuif, , France

Local Institution - 455

Dresden, Saxony, Germany

Local Institution - 451

Berlin, , Germany

Local Institution - 450

Cologne, , Germany

Local Institution - 452

Hamburg, , Germany

Local Institution - 453

München, , Germany

Local Institution - 454

Münster, , Germany

Local Institution - 500

Rome, , Italy

Local Institution - 501

Rozzano (MI), , Italy

Local Institution - 502

Torino, , Italy

Local Institution - 203

Osaka, Osaka-shi, Japan

Local Institution - 200

Chuo-ku, Tokyo, Japan

Local Institution - 201

Minato-ku, Tokyo, Japan

Local Institution - 202

Bunkyō City, , Japan

Local Institution - 550

Rotterdam, , Netherlands

Local Institution - 600

Barcelona, , Spain

Local Institution - 601

Madrid, , Spain

Local Institution - 650

Stockholm, , Sweden

Local Institution - 700

Bern, , Switzerland

Local Institution - 751

Southampton, Hampshire, United Kingdom

Local Institution - 750

London, , United Kingdom

Countries

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

References

Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Chow VA, Montheard S, Santamaria J, Colicino S, Ogasawara K, Stepan L, Liu FF, Abramson JS. Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study. J Clin Oncol. 2025 Aug 20;43(24):2671-2678. doi: 10.1200/JCO-25-00399. Epub 2025 Jul 7.

Reference Type: DERIVED

PMID: 40623279 (View on PubMed)

Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M. Plain language summary of the TRANSFORM study primary analysis results: liso-cell as a second treatment regimen for large B-cell lymphoma following failure of the first treatment regimen. Future Oncol. 2024;20(21):1455-1465. doi: 10.2217/fon-2023-0898. Epub 2024 Mar 28.

Reference Type: DERIVED

PMID: 38547003 (View on PubMed)

Saeedian M, Badaracco J, Botros A, Gitlin M, Keating SJ. Estimating the Cost per Clinical Outcome of Second-Line Liso-Cel Versus Autologous Stem Cell Transplantation in Patients with Transplantation-Intended Relapsed/Refractory Large B Cell Lymphoma. Transplant Cell Ther. 2023 Nov;29(11):712.e1-712.e7. doi: 10.1016/j.jtct.2023.08.001. Epub 2023 Aug 5.

Reference Type: DERIVED

PMID: 37544410 (View on PubMed)

Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182/blood.2022018730.

Reference Type: DERIVED

PMID: 36542826 (View on PubMed)

Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6.

Reference Type: DERIVED

PMID: 35717989 (View on PubMed)

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Thiruvengadam SK, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.

Reference Type: DERIVED

PMID: 33288485 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

U1111-1213-1944

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-000929-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JCAR017-BCM-003

Identifier Type: -

Identifier Source: org_study_id