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Non-Hodgkin LymphomaPhase 1NCT02631044

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

A Phase 1 study testing JCAR017 (lisocabtagene maraleucel) single-dose schedule and JCAR017 (lisocabtagene maraleucel) 2-dose schedule in people with Non-Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
JCAR017 (lisocabtagene maraleucel) single-dose schedule and JCAR017 (lisocabtagene maraleucel) 2-dose schedule
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
387 participants
Where
14 sitesUnited States
Study dates
6 Jan 2016to 16 May 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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.

Who cannot join

  • 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)
Show all 22Show fewer
  • 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
  • Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017 administration (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolyate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti IL6, or anti-IL6R)
  • Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration
  • Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to leukapheresis.
  • Allo-HSCT within 90 days of leukapheresis
  • Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment
  • Progressive vascular tumor invasion, thrombosis, or embolism
  • Venous thrombosis or embolism not managed on a stable regimen of anticoagulation

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Local Institution - 0019

    Atlanta, Georgia, 30342

  • Local Institution - 0020

    Aurora, Colorado, 80045

  • Local Institution - 0006

    Birmingham, Alabama, 35294

  • Local Institution - 0005

    Boston, Massachusetts, 02114

  • Local Institution - 0015

    Boston, Massachusetts, 02115

  • Local Institution - 0021

    Charlotte, North Carolina, 28204

  • Local Institution - 0003

    Chicago, Illinois, 60611

  • Local Institution - 0007

    Duarte, California, 91010-300

  • Local Institution - 0002

    Houston, Texas, 77030

  • Local Institution - 0001

    New York, New York, 10065

  • Local Institution - 0008

    Omaha, Nebraska, 68198-7680

  • Local Institution - 0029

    Pittsburgh, Pennsylvania, 15232

  • Local Institution - 0010

    San Francisco, California, 94143-0372

  • Local Institution - 0018

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)

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.

Read the detailed description

This is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics (PK), and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma Grade 3B, and mantle cell lymphoma (MCL). This study will evaluate and refine the dose and schedule of JCAR017 to optimize safety and antitumor activity. A dose-confirmation group or groups will further evaluate the safety and efficacy of JCAR017 at the recommended regimen(s).

Upon successful generation of JCAR017 product, participants will receive treatment with one or more cycles of JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one or two doses of JCAR017 administered by intravenous (IV) injection.

The follow-up period for each participant is approximately 24 months after the final JCAR017 infusion. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR017 infusion.

Being tested
JCAR017 (lisocabtagene maraleucel) single-dose schedule, JCAR017 (lisocabtagene maraleucel) 2-dose schedule
Keywords
JCAR017, chimeric antigen receptor, non-Hodgkin lymphoma, CAR, CAR T cells, autologous T cell therapy, cell therapy, NHL
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • JCAR017 (lisocabtagene maraleucel) single-dose scheduleBiological

    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 (lisocabtagene maraleucel) 2-dose scheduleBiological

    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.

Study groups in NCT02631044
Study groupRoleWhat they receive
JCAR017 1-dose scheduleExperimentalEach cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection
Receives: Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule
JCAR017 2-dose schedule (no longer accruing)ExperimentalEach cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections
Receives: Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Physiological parameter

    Measured: Up to 730 days after the final JCAR017 infusion

  2. Dose-limiting toxicities of JCAR017

    Physiological parameter

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

  3. Objective response rate (ORR)

    Lugano criteria

    Measured: 24 months

Secondary outcomes (8)

  1. Complete response (CR) rate

    Lugano criteria

    Measured: 24 months

  2. Duration of response

    Lugano criteria

    Measured: 24 months

  3. Progression-free survival (PFS)

    Lugano criteria

    Measured: 24 months

  4. Overall survival

    Physiological parameter

    Measured: Up to 15 years

  5. Health-related quality of life

    Questionnaire

    Measured: 24 months

  6. Maximum concentration of JCAR017 (Cmax) in the peripheral blood

    qPCR

    Measured: Up to 365 days after the final JCAR017 infusion

  7. Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood

    qPCR

    Measured: Up to 365 days after the final JCAR017 infusion

  8. Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood

    qPCR

    Measured: Up to 365 days after the final JCAR017 infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2015 (estimated)
  2. Study start6 Jan 2016
  3. Primary completion16 May 2024
  4. Study completion16 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
387 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02631044
Sponsor's protocol ID
017001
Status last verified
Jun 2024
First submitted
11 Dec 2015
Last updated
27 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Abramson JS, Siddiqi T, Gordon LI, Lunning MA, Wang M, Arnason JE, Kamdar M, Maloney DG, Shadman M, Andreadis CB, Sehgal A, Solomon SR, Ghosh N, Hidalgo-Lopez JE, Wang J, Ding X, Ogasawara K, Singh A, Palomba ML. Five-year survival outcomes from TRANSCEND NHL 001 of lisocabtagene maraleucel in R/R LBCL. Blood. 2026 Jun 3:blood.2025032270. doi: 10.1182/blood.2025032270. Online ahead of print.

    PubMed 42237652

  • 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.

    PubMed 38072625

  • 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.

    PubMed 37890149

  • 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.

    PubMed 36755418

  • 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.

    PubMed 35610089

  • 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.

    PubMed 35337365

  • 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.

    PubMed 35156195

  • 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.

    PubMed 34515338

  • 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.

    PubMed 34493319

  • 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.

    PubMed 34310745

  • 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.

    PubMed 34125421

  • 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.

    PubMed 33970454

  • 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.

    PubMed 33904895

  • 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.

    PubMed 33720336

  • 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.

    PubMed 32888407

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing JCAR017 (lisocabtagene maraleucel) single-dose schedule and JCAR017 (lisocabtagene maraleucel) 2-dose schedule in people with Non-Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-related adverse events (AEs) as assessed by CTCAE v4.03 (time frame: Up to 730 days after the final JCAR017 infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02631044, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2024.

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