Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma (TRANSCENDWORLD)

A Phase 2, Single-arm, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or With Other Aggressive B-Cell Malignancies

The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: JCAR017

Detailed Description

This is a study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell NHL. The study will enroll participants in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Participants with secondary central nervous system (CNS) involvement are allowed.

Once enrolled, participants will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, participants will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered by intravenous infusion. Participants will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life.

Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Local Institution - 101
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 351
• Finland
  • Helsinki, Finland, 00029
    • Local Institution - 551
• France
  • Lille, France, 59037
    • Local Institution - 202
  • Paris Cedex 10, France, 75475
    • Local Institution - 203
  • Pierre Benite cedex, France, 69495
    • Local Institution - 201
• Germany
  • Dresden, Germany, 01307
    • Local Institution - 152
  • Heidelberg, Germany, 69120
    • Local Institution - 155
  • Köln, Germany, 50937
    • Local Institution - 151
  • München, Germany, 81377
    • Local Institution - 154
  • Ulm, Germany, 89081
    • Local Institution - 153
• Italy
  • Milan, Italy, 20133
    • Local Institution - 402
  • Torino, Italy, 10126
    • Local Institution - 401
• Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Local Institution - 601
    • Minato-ku, Tokyo, Japan, 105-8470
      • Local Institution - 602
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Local Institution - 301
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 451
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 251
• United Kingdom
  • London, United Kingdom, WC1E 6BT
    • Local Institution - 501
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M20 4BX
      • Local Institution - 502

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmation of diagnosis at last relapse
• Adequate organ function
• Adequate vascular access for leukapheresis procedure

Exclusion Criteria:

• Prior history of malignancies, other than aggressive relapsed/refractory Non-Hodgkin Lymphoma, unless the participant has been in remission for ≥ 2 years with the exception of non-invasive malignancies
• Received previous CD19-targeted therapy
• Progressive vascular tumor invasion, thrombosis, or embolism

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of JCAR017	Drug: JCAR017; Specified dose on specified days; Other Names: Lisocabtagene Maraleucel (liso-cel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR) of JCAR017 in participants with Non-Hodgkin Lymphoma (NHL; including secondary central nervous system (CNS) involvement)	Up to 2 years after JCAR017 infusion
ORR of JCAR017 in participants with relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL)	Up to 2 years after JCAR017 infusion
Adverse Events (AEs) in participants intended to be treated as outpatients	Up to 2 years after JCAR017 infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events	Up to 2 years after JCAR017 infusion
Incidence of Serious Adverse Events	Up to 2 years after JCAR017 infusion
Incidence of clinically significant changes in clinical laboratory results: Hematology tests	Up to 2 years after JCAR017 infusion
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests	Up to 2 years after JCAR017 infusion
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests	Up to 2 years after JCAR017 infusion
Adverse Events (AEs) in participants treated as outpatients	Up to 2 years after JCAR017 infusion
Overall Response Rate (ORR) in participants intended to be treated as outpatients	Up to 2 years after JCAR017 infusion
Complete Response Rate (CRR)	Up to 2 years after JCAR017 infusion
Event-free survival (EFS)	Up to 2 years after JCAR017 infusion
Progression-free survival (PFS)	Up to 2 years after JCAR017 infusion
Overall survival (OS)	Up to last participant last visit (approximately 40 months)
Duration of response (DOR)	Up to 2 years after JCAR017 infusion
Pharmacokinetics by quantitative polymerase chain reaction (qPCR) - Maximum plasma concentration of drug (Cmax)	Up to 2 years after JCAR017 infusion
Pharmacokinetics by qPCR - Time to peak concentration (Tmax)	Up to 2 years after JCAR017 infusion
Pharmacokinetics by qPCR - Area under the curve (AUC)	Up to 2 years after JCAR017 infusion
Patient-Reported Outcomes - European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire	Up to 2 years after JCAR017 infusion
Patient-Reported Outcomes - Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale	Up to 2 years after JCAR017 infusion

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2018
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: JCAR017; Diffuse large B-cell lymphoma; Non-Hodgkin lymphoma; Primary central nervous system lymphoma; Aggressive B-cell non-Hodgkin lymphoma; Relapse / refractory lymphoma; Transplant not eligible; High-grade B-cell lymphoma; Transformed follicular lymphoma; Follicular lymphoma Grade 3B; Liso-Cel
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Aggression; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: JCAR017-BCM-001; U1111-1209-4055 (Other Grant/Funding Number: WHO); 2017-000106-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes