Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)

NCT02631044 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 017001
• Study Type: interventional
• Target: 387
• Locations: 1 country
• Sites: 14

Brief Summary

This open-label Phase 1 study will evaluate the safety, PK, and antitumor activity of modified T cells (JCAR017) administered to adult patients with relapsed or refractory B-cell NHL. The dose and schedule of JCAR017 will be evaluated and modified, as needed, for safety and antitumor activity. We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma whose disease has come back or has not responded to treatment.

Conditions

Non-Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Mantle-cell Lymphoma; Primary Mediastinal B-cell Lymphoma

Keywords

JCAR017; chimeric antigen receptor; non-Hodgkin lymphoma; CAR; CAR T cells; autologous T cell therapy; cell therapy; NHL

Outcome Measures

Primary Outcomes (3)

• Treatment-related adverse events (AEs) as assessed by CTCAE v4.03

  Physiological parameter

  Up to 730 days after the final JCAR017 infusion

• Dose-limiting toxicities of JCAR017

  Physiological parameter

  28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion

• Objective response rate (ORR)

  Lugano criteria

  24 months

Secondary Outcomes (8)

• Complete response (CR) rate

  24 months

• Duration of response

  24 months

• Progression-free survival (PFS)

  24 months

• Overall survival

  Up to 15 years

• Health-related quality of life

  24 months

Study Arms (2)

JCAR017 1-dose schedule

EXPERIMENTAL

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection

Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule

JCAR017 2-dose schedule (no longer accruing)

EXPERIMENTAL

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections

Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule

Interventions

JCAR017 (lisocabtagene maraleucel) single-dose schedule BIOLOGICAL

Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.

JCAR017 1-dose schedule

JCAR017 (lisocabtagene maraleucel) 2-dose schedule BIOLOGICAL

Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon product availability, participants will receive study treatment consisting of lymphodepleting chemotherapy followed by two IV doses of JCAR017.

JCAR017 2-dose schedule (no longer accruing)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Relapsed or refractory B-cell NHL, including
• DLBCL cohort (no longer enrolling): DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology \[tDLBCL\]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of systemic therapy or after auto-HSCT.
• MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization \[FISH\], or PCR) with relapsed or refractory disease after at least 2 prior lines of systemic MCL therapy. Subjects must have been treated with an alkylating agent, Bruton's tyrosine kinase inhibitor (BTKi), and rituximab (or other CD20-targeted agent).
• PET-positive disease by Lugano classification
• Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
• Adequate vascular access for leukapheresis procedure
• Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.
• Participants must agree to use appropriate contraception.

You may not qualify if:

• Active central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study)
• History of other primary malignancy not in remission for at least 2 years (The following are exempt from the 2-year limit: nonmelanoma skin cancer, definitively treated stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
• Treatment with alemtuzumab within 6 months of leukapheresis or fludarabine or cladribine within 3 months of leukapheresis
• Active hepatitis B, hepatitis C, or Subjects with a history of or active human immunodeficiency virus (HIV) infectionare excluded. Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a negative 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
• Uncontrolled systemic fungal, bacterial, viral, or other infection
• Presence of graft-vs-host disease (GVHD)
• History of cardiovascular disease
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Pregnant or nursing women
• Use of the following:
• Therapeutic doses of corticosteroids (defined as \>20 mg/day prednisone or equivalent) within 7 days of leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, topical, and inhaled steroids are permitted.
• Low dose chemotherapy (e.g., vincristine, rituximab, cyclophosphamide ≤300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥7 days prior to lymphodepleting chemotherapy.
• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
• Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) within 2 weeks of leukapheresis.
• Experimental agents within 4 weeks of leukapheresis unless no response or disease progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis

Sponsors & Collaborators

• Juno Therapeutics, a Subsidiary of Celgene: lead

Study Sites (14)

Local Institution - 0006

Birmingham, Alabama, 35294, United States

Location

Local Institution - 0007

Duarte, California, 91010-300, United States

Location

Local Institution - 0010

San Francisco, California, 94143-0372, United States

Location

Local Institution - 0020

Aurora, Colorado, 80045, United States

Location

Local Institution - 0019

Atlanta, Georgia, 30342, United States

Location

Local Institution - 0003

Chicago, Illinois, 60611, United States

Location

Local Institution - 0005

Boston, Massachusetts, 02114, United States

Location

Local Institution - 0015

Boston, Massachusetts, 02115, United States

Location

Local Institution - 0008

Omaha, Nebraska, 68198-7680, United States

Location

Local Institution - 0001

New York, New York, 10065, United States

Location

Local Institution - 0021

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0029

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 0002

Houston, Texas, 77030, United States

Location

Local Institution - 0018

Seattle, Washington, 98109, United States

Location

Related Publications (14)

• Wang M, Siddiqi T, Gordon LI, Kamdar M, Lunning M, Hirayama AV, Abramson JS, Arnason J, Ghosh N, Mehta A, Andreadis C, Solomon SR, Kostic A, Dehner C, Espinola R, Peng L, Ogasawara K, Chattin A, Eliason L, Palomba ML. Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study. J Clin Oncol. 2024 Apr 1;42(10):1146-1157. doi: 10.1200/JCO.23.02214. Epub 2023 Dec 10.

  PMID: 38072625 DERIVED

• Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Dehner C, Kim Y, Ogasawara K, Kostic A, Siddiqi T. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024 Feb 1;143(5):404-416. doi: 10.1182/blood.2023020854.

  PMID: 37890149 DERIVED

• Van Le H, Van Naarden Braun K, Nowakowski GS, Sermer D, Radford J, Townsend W, Ghesquieres H, Menne T, Porpaczy E, Fox CP, Schusterbauer C, Liu FF, Yue L, De Benedetti M, Hasskarl J. Use of a real-world synthetic control arm for direct comparison of lisocabtagene maraleucel and conventional therapy in relapsed/refractory large B-cell lymphoma. Leuk Lymphoma. 2023 Mar;64(3):573-585. doi: 10.1080/10428194.2022.2160200. Epub 2023 Feb 8.

  PMID: 36755418 DERIVED

• Teoh J, Brown LF. Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. Cytotherapy. 2022 Sep;24(9):962-973. doi: 10.1016/j.jcyt.2022.03.013. Epub 2022 May 21.

  PMID: 35610089 DERIVED

• Cartron G, Fox CP, Liu FF, Kostic A, Hasskarl J, Li D, Bonner A, Zhang Y, Maloney DG, Kuruvilla J. Matching-adjusted indirect treatment comparison of chimeric antigen receptor T-cell therapies for third-line or later treatment of relapsed or refractory large B-cell lymphoma: lisocabtagene maraleucel versus tisagenlecleucel. Exp Hematol Oncol. 2022 Mar 25;11(1):17. doi: 10.1186/s40164-022-00268-z.

  PMID: 35337365 DERIVED

• Ogasawara K, Lymp J, Mack T, Dell'Aringa J, Huang CP, Smith J, Peiser L, Kostic A. In Vivo Cellular Expansion of Lisocabtagene Maraleucel and Association With Efficacy and Safety in Relapsed/Refractory Large B-Cell Lymphoma. Clin Pharmacol Ther. 2022 Jul;112(1):81-89. doi: 10.1002/cpt.2561. Epub 2022 Mar 20.

  PMID: 35156195 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

• Maloney DG, Kuruvilla J, Liu FF, Kostic A, Kim Y, Bonner A, Zhang Y, Fox CP, Cartron G. Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. J Hematol Oncol. 2021 Sep 8;14(1):140. doi: 10.1186/s13045-021-01144-9.

  PMID: 34493319 DERIVED

• Westin JR, Kersten MJ, Salles G, Abramson JS, Schuster SJ, Locke FL, Andreadis C. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021 Oct 1;96(10):1295-1312. doi: 10.1002/ajh.26301. Epub 2021 Aug 13.

  PMID: 34310745 DERIVED

• Ogasawara K, Dodds M, Mack T, Lymp J, Dell'Aringa J, Smith J. Population Cellular Kinetics of Lisocabtagene Maraleucel, an Autologous CD19-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed/Refractory Large B-Cell Lymphoma. Clin Pharmacokinet. 2021 Dec;60(12):1621-1633. doi: 10.1007/s40262-021-01039-5. Epub 2021 Jun 14.

  PMID: 34125421 DERIVED

• Salles G, Spin P, Liu FF, Garcia J, Kim Y, Hasskarl J. Indirect Treatment Comparison of Liso-Cel vs. Salvage Chemotherapy in Diffuse Large B-Cell Lymphoma: TRANSCEND vs. SCHOLAR-1. Adv Ther. 2021 Jun;38(6):3266-3280. doi: 10.1007/s12325-021-01756-0. Epub 2021 May 10.

  PMID: 33970454 DERIVED

• Patrick DL, Powers A, Jun MP, Kim Y, Garcia J, Dehner C, Maloney DG. Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma. Blood Adv. 2021 Apr 27;5(8):2245-2255. doi: 10.1182/bloodadvances.2020003503.

  PMID: 33904895 DERIVED

• Abramson JS, Siddiqi T, Garcia J, Dehner C, Kim Y, Nguyen A, Snyder S, McGarvey N, Gitlin M, Pelletier C, Jun MP. Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel-treated patients in the TRANSCEND NHL 001 trial. Blood Adv. 2021 Mar 23;5(6):1695-1705. doi: 10.1182/bloodadvances.2020003531.

  PMID: 33720336 DERIVED

• Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. doi: 10.1016/S0140-6736(20)31366-0. Epub 2020 Sep 1.

  PMID: 32888407 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

Appointments and Schedules

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Organization and Administration; Health Services Administration

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 15, 2015
• Study Start: January 6, 2016
• Primary Completion: May 16, 2024
• Study Completion: May 16, 2024
• Last Updated: June 27, 2024

Record last verified: 2024-06

Locations

US (14)