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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: JCAR017


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of JCAR017<br> | Drug: JCAR017<br>* Specified dose on specified days<br>* Other names: Lisocabtagene Maraleucel (liso-cel);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin lymphoma, Aggressive B-cell non-Hodgkin lymphoma, Diffuse large B-cell lymphoma, Relapse / refractory lymphoma, Transplant not eligible, High-grade B-cell lymphoma, Primary central nervous system lymphoma, Transformed follicular lymphoma, Follicular lymphoma Grade 3B, JCAR017, Liso-Cel