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

NCT03575351 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: JCAR017-BCM-003U1111-1213-19442018-000929-32
• Study Type: interventional
• Target: 184
• Locations: 12 countries
• Sites: 54

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

Keywords

Non-Hodgkin Lymphomas; DLBCL; Efficacy; Safety; JCAR017; Liso-cel; High-Risk; Relapsed; Refractory; B-cell NHL

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS) Per Independent Review Committee (IRC)

  Time from randomization to death, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR) by 9 weeks or start of new antineoplastic therapy, whichever occurs first. CR: Target nodes masses must regress to ≤ 1.5cm in LDi, no extralymphatic sites, no new lesions. PR: ≥ 50% decrease in sum of diameters of up to 6 target nodes and extranodal sites, no new lesions, spleen must have regressed \> 50% in length. PD: LDi \> 1.5cm, increase by ≥ 50% from PPD nadir, an increase in LDi or SDi from nadir, 0.5 cm for lesions ≤ 2cm, 1.0cm for lesions \> 2cm. Complete metabolic response: Lymph nodes score 1, 2, 3 with/without residual mass on 5-point scale, no new lesions, no FDG-avid disease. Partial metabolic response: Lymph nodes score 4 or 5, reduced uptake from baseline, no new lesions, residual uptake higher than normal, reduced from baseline. Progressive metabolic disease: Score 4 or 5 with an increase in uptake intensity from baseline and/or new FDG-avid.

  From randomization to death from any cause, PD, failure to achieve CR or PR by 9 weeks post randomization, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first (Up to 36 months)

Secondary Outcomes (25)

• Complete Response Rate (CRR)

  From randomization up to 3 years post randomization (Up to 36 months)

• Number of Participants With Complete Response (CR)

  From randomization up to 3 years post randomization (Up to 36 months)

• Progression-free Survival (PFS)

  From randomization to progression, or death from any cause, whichever occurs first (Up to 36 months)

• Overall Survival (OS)

  From randomization to time of death due to any cause (Up to 36 months)

• Overall Response Rate (ORR)

  From randomization to PR or CR (Up to 36 months)

Study Arms (2)

Arm A - Standard of Care (SOC)

ACTIVE COMPARATOR

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

Arm B - JCAR017

EXPERIMENTAL

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

Interventions

Standard of Care DRUG

Standard of Care

Arm A - Standard of Care (SOC)

JCAR017 GENETIC

JCAR017

Also known as: lisocabtagene maraleucel or liso-cel

Arm B - JCAR017

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• 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.
• Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
• \[18F\] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
• Adequate organ function
• Participants must agree to use effective contraception

You may not qualify if:

• Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
• Subjects planned to undergo allogeneic stem cell transplantation.
• 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).
• 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
• Treatment with any prior gene therapy product.
• Subjects who have received previous CD19-targeted therapy.
• 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.
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
• Active autoimmune disease requiring immunosuppressive therapy.

Sponsors & Collaborators

• Celgene: lead

Study Sites (54)

Local Institution - 129

Scottsdale, Arizona, 85258, United States

Location

Local Institution - 116

Scottsdale, Arizona, 85259, United States

Location

Local Institution - 115

San Francisco, California, 94143, United States

Location

Local Institution - 106

Aurora, Colorado, 80045, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Local Institution - 126

Tampa, Florida, 33612, United States

Location

Local Institution - 108

Atlanta, Georgia, 30322, United States

Location

Local Institution - 107

Atlanta, Georgia, 30342, United States

Location

Local Institution - 122

Chicago, Illinois, 60611, United States

Location

Loyola University Medical Center Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Local Institution - 102

Boston, Massachusetts, 02114, United States

Location

Local Institution - 104

Boston, Massachusetts, 02215, United States

Location

Local Institution - 120

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 119

Detroit, Michigan, 48201, United States

Location

Local Institution - 112

Minneapolis, Minnesota, 55455, United States

Location

Local Institution - 103

Rochester, Minnesota, 55905-0001, United States

Location

Local Institution - 100

Omaha, Nebraska, 68198, United States

Location

Local Institution - 121

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 111

Buffalo, New York, 14263, United States

Location

Local Institution - 117

New York, New York, 10065, United States

Location

Local Institution - 125

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 127

Oklahoma City, Oklahoma, 73104, United States

Location

Local Institution - 101

Portland, Oregon, 97239, United States

Location

Local Institution - 123

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 109

Dallas, Texas, 75246, United States

Location

Local Institution - 124

Houston, Texas, 77030, United States

Location

Local Institution - 114

Richmond, Virginia, 23298, United States

Location

Local Institution - 110

Seattle, Washington, 98109-4417, United States

Location

Local Institution - 350

Ghent, 9000, Belgium

Location

Local Institution - UNK 25

Helsinki, 00029, Finland

Location

Local Institution - 401

Lille, 59037, France

Location

Local Institution - 400

Marseille, 13273, France

Location

Local Institution - 403

Pierre-Bénite, 69495, France

Location

Local Institution - 402

Villejuif, 94805, France

Location

Local Institution - 455

Dresden, Saxony, 01307, Germany

Location

Local Institution - 451

Berlin, 13125, Germany

Location

Local Institution - 450

Cologne, 50937, Germany

Location

Local Institution - 452

Hamburg, 20246, Germany

Location

Local Institution - 453

München, 81377, Germany

Location

Local Institution - 454

Münster, 48149, Germany

Location

Local Institution - 500

Rome, 00161, Italy

Location

Local Institution - 501

Rozzano (MI), 20089, Italy

Location

Local Institution - 502

Torino, 10126, Italy

Location

Local Institution - 203

Osaka, Osaka-shi, 545-8586, Japan

Location

Local Institution - 200

Chuo-ku, Tokyo, 104-0045, Japan

Location

Local Institution - 201

Minato-ku, Tokyo, 105-8470, Japan

Location

Local Institution - 202

Bunkyō City, 113-8677, Japan

Location

Local Institution - 550

Rotterdam, 3075 EA, Netherlands

Location

Local Institution - 600

Barcelona, 08036, Spain

Location

Local Institution - 601

Madrid, 28041, Spain

Location

Local Institution - 650

Stockholm, SE-141 86, Sweden

Location

Local Institution - 700

Bern, 3010, Switzerland

Location

Local Institution - 751

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Local Institution - 750

London, WC1E 6AG, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 40623279 DERIVED

• 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.

  PMID: 38547003 DERIVED

• 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.

  PMID: 37544410 DERIVED

• 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.

  PMID: 36542826 DERIVED

• 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.

  PMID: 35717989 DERIVED

• 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.

  PMID: 34515338 DERIVED

• 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.

  PMID: 33288485 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 2, 2018
• Study Start: October 23, 2018
• Primary Completion: October 23, 2023
• Study Completion: October 23, 2023
• Last Updated: August 3, 2025
• Results First Posted: August 3, 2025

Record last verified: 2025-07

Locations

BE (1); JP (4); ES (2); SE (1); CH (1); FR (4); GB (2); NL (1); US (28); FI (1); IT (3); DE (6)