A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)

NCT03744676 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 017007
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 23

Brief Summary

This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Disorder

Keywords

Lisocabtagene maraleucel; liso-cel; JCAR017; relapse; refractory; B-Cell Non-Hodgkin Lymphoma; NHL; chimeric antigen receptor; CAR; CAR T cell; autologous T cell therapy; immunotherapy; cell therapy; B-cell malignancies

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3

  Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).

  From first dose to 90 days following first dose (up to approximately 90 days)

• Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3

  NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity. Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.

  From first dose to 90 days following first dose (up to approximately 90 days)

• Percentage of Participants With Infection Adverse Events Grade ≥ 3

  Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.

  From first dose to 90 days following first dose (up to approximately 90 days)

• Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29.

  Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.

  At Day 29 after first treatment

Secondary Outcomes (22)

• Number of Participants With Adverse Events

  From first dose to 90 days following first dose (up to approximately 90 days)

• Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology

  From first dose to up to 41 months

• Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry

  From first dose to up to 41 months

• Number of Participants With Adverse Events Grade ≥ 3

  From first dose to 90 days following first dose (up to approximately 90 days)

• Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)

  From first dose to up to approximately 41 months

Study Arms (1)

Lisocabtagene maraleucel

EXPERIMENTAL

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.

Biological: lisocabtagene maraleucel

Interventions

lisocabtagene maraleucel BIOLOGICAL

lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection

Also known as: JCAR017, liso-cel

Lisocabtagene maraleucel

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 at the time of consent
• Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL from indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, 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 systemic lines of therapy for DLBCL or after auto-HSCT.
• Positron-emission tomography-positive disease by Lugano Classification
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function
• Adequate vascular access for leukapheresis procedure
• Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
• Subjects must agree to use appropriate contraception.

You may not qualify if:

• Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
• History of prior allogeneic hematopoietic stem cell transplant
• Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
• History of another primary malignancy that has not been in remission for at least 2 years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on a Papanicolau smear.
• Active hepatitis B or hepatitis C infection at the time of screening
• History of or active human immunodeficiency virus infection at the time of screening
• Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or lisocabtagene maraleucel administration
• Presence of acute or chronic graft-versus-host disease
• History of clinically significant cardiac conditions within the past 6 months
• History or presence of clinically relevant CNS pathology such as epilepsy/seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Pregnant or nursing women
• Subject does not meet protocol-specified washout periods for certain prior treatments
• Prior CAR T-cell or other genetically modified T-cell therapy
• Progressive vascular tumor invasion, thrombosis, or embolism
• Venous thrombosis or embolism not managed on stable regimen of anticoagulation

Sponsors & Collaborators

• Juno Therapeutics, a Subsidiary of Celgene: lead
• Bristol-Myers Squibb: collaborator

Study Sites (23)

Local Institution - 0057

Los Angeles, California, 90048, United States

Location

Local Institution - 0060

Denver, Colorado, 80218, United States

Location

Local Institution - 0089

Miami, Florida, 33176, United States

Location

Local Institution - 0081

Orlando, Florida, 32804, United States

Location

Local Institution - 0065

Indianapolis, Indiana, 46237, United States

Location

Local Institution - 0069

Wichita, Kansas, 67124, United States

Location

Local Institution - 0064

Louisville, Kentucky, 40207, United States

Location

Local Institution - 0101

Southfield, Michigan, 48075, United States

Location

Local Institution - 0052

East Brunswick, New Jersey, 08816, United States

Location

Local Institution - 0066

Morristown, New Jersey, 07962, United States

Location

Local Institution - 0041

Albany, New York, 12208, United States

Location

Local Institution - 0039

Cincinnati, Ohio, 45236, United States

Location

Local Institution - 0098

Eugene, Oregon, 97401, United States

Location

Local Institution - 0051

Portland, Oregon, 97213, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Local Institution - 0037

Greenville, South Carolina, 29615, United States

Location

Local Institution - 0063

Nashville, Tennessee, 37203, United States

Location

Local Institution - 0097

Dallas, Texas, 75230, United States

Location

Local Institution - 0061

San Antonio, Texas, 78229, United States

Location

Baylor Scott and White Health

Temple, Texas, 76508, United States

Location

Local Institution - 0096

Tyler, Texas, 75702, United States

Location

Local Institution - 0074

Salt Lake City, Utah, 84143, United States

Location

Local Institution - 0036

Norfolk, Virginia, 23502, United States

Location

Related Publications (2)

• Linhares Y, Freytes CO, Cherry M, Bachier C, Maris M, Hoda D, Varela JC, Bellomo C, Cross S, Essell J, Fanning S, Terebelo H, Yimer H, Courtright J, Sharman JP, Kostic A, Vedal M, Ogasawara K, Avilion A, Espinola R, Yuan B, Mattar B. OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL. Blood Adv. 2024 Dec 10;8(23):6114-6126. doi: 10.1182/bloodadvances.2024013254.

  PMID: 39347584 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

Related Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Recurrence

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

Clinical.Trials@bms.com

1-855-907-3286

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 16, 2018
• Study Start: November 29, 2018
• Primary Completion: September 22, 2023
• Study Completion: September 22, 2023
• Last Updated: February 27, 2025
• Results First Posted: December 6, 2023

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (23)