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

• ClinicalTrials.gov Identifier: NCT03484702
• Recruitment Status: Completed
• First Posted: April 2, 2018
• Last Update Posted: January 12, 2024
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: March 26, 2018
• First Posted Date: April 2, 2018
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: September 7, 2018
• Actual Primary Completion Date: December 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2022)

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

Original Primary Outcome Measures (submitted: March 26, 2018)

• Overall Response Rate (ORR) of JCAR017 in subjects with Non-Hodgkin Lymphoma (NHL; including secondary central nervous system (CNS) involvement) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Proportion of subjects achieving a complete response (CR) or partial response (PR) based on the Lugano classification (Cheson, 2014)
• ORR of JCAR017 in subjects with relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Proportion of subjects achieving a CR/complete response unconfirmed (CRu) or PR based on the International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma (Abrey, 2005)

Current Secondary Outcome Measures (submitted: January 21, 2022)

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

Original Secondary Outcome Measures (submitted: March 26, 2018)

• Adverse Events (AEs) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Type, frequency, and severity of AEs, including serious adverse events (SAEs) and laboratory abnormalities
• Overall Response Rate (ORR)on the underlying chronic lymphocytic leukemia (CLL) in subjects with Richter´s transformation [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Proportion of subjects achieving a CR, CR with incomplete bone marrow recovery (CRi), nodular PR (nPR), PR or PR with lymphocytosis (PRL) based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines
• Complete response rate (CRR) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Proportion of subjects achieving a CR (or CR and CRu for subjects with PCNSL) following JCAR017 infusion
• Event-free survival (EFS) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Time from JCAR017 infusion to death from any cause, progressive disease (PD), or starting a new anticancer therapy, whichever occurs first
• Progression-free survival (PFS) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Time from JCAR017 infusion to the first documentation of PD, or death due to any cause, whichever occurs first
• Overall survival (OS) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Time from JCAR017 infusion to time of death due to any cause
• Duration of response (DOR) [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Time from first response to progressive disease or death from any cause, whichever occurs first
• Pharmacokinetic - Cmax [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Maximum concentration
• Pharmacokinetic - Tmax [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Time to peak concentration
• Pharmacokinetic - AUC [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Area under the curve
• Patient-Reported Outcomes - EORTC QLQ-C30 [ Time Frame: Up to 2 years after JCAR017 infusion ]
  European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire: The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of life.
• Patient-Reported Outcomes - EQ-5D-5L [ Time Frame: Up to 2 years after JCAR017 infusion ]
  European Quality of Life-5 Dimensions health state classifier to 5 Levels questionnaire: EQ-5D is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal.
• Patient-Reported Outcomes - FACT-Lym [ Time Frame: Up to 2 years after JCAR017 infusion ]
  Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale: Only the LYM subscale will be administered in this study. This scale addresses symptoms and functional limitations (15 item) that are important to lymphoma patients.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma
• Official Title: 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
• Brief Summary: 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)

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma, Non-Hodgkin

Intervention

Drug: JCAR017

Specified dose on specified days

Other Name: Lisocabtagene Maraleucel (liso-cel)

Study Arms

Experimental: Administration of JCAR017

Intervention: Drug: JCAR017

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2024): 113
• Original Estimated Enrollment (submitted: March 26, 2018): 124
• Actual Study Completion Date: December 15, 2023
• Actual Primary Completion Date: December 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Finland, France, Germany, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT03484702
• Other Study ID Numbers: JCAR017-BCM-001; U1111-1209-4055 ( Other Grant/Funding Number: WHO ); 2017-000106-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: January 2024