Clinical trial NCT03484702: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Keywords: 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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2018-04-02
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate (ORR) Per Independent Review Committee in Cohorts 1, 2 and 3
timeFrame: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Overall Response Rate (ORR) Per Investigator in Cohort 4
timeFrame: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Overall Response Rate (ORR) Per Investigator in Cohort 5
timeFrame: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Number of Participants With Adverse Events in Cohort 7
timeFrame: From leukapheresis to end of study (up to approximately 63 months)
measure: Number of Participants With Serious Adverse Events (SAEs) in Cohort 7
timeFrame: From leukapheresis to end of study (up to approximately 63 months)
measure: Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohort 7
timeFrame: At Baseline and Day 29 after JCAR017 infusion
measure: Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohort 7
timeFrame: At Baseline and Day 29 after JCAR017 infusion
Secondary outcomes:
measure: Number of Participants With Adverse Events in Cohorts 1, 2, 3, 4, and 5
timeFrame: From leukapheresis to end of study (up to approximately 63 months)
measure: Number of Participants With Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5
timeFrame: From leukapheresis to end of study (up to approximately 63 months)
measure: Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5
timeFrame: At Baseline and Day 29 after JCAR017 infusion
measure: Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5
timeFrame: At Baseline and Day 29 after JCAR017 infusion
measure: Overall Response Rate (ORR) in Cohort 7
timeFrame: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Complete Response Rate (CRR)
timeFrame: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Event Free Survival (EFS)
timeFrame: From JCAR017 infusion to death due to any reason, progressive disease, or starting a new anticancer therapy (up to approximately 63 months).
measure: Progression Free Survival (PFS) Using European Medicines Agency (EMA) Criteria
timeFrame: From JCAR017 infusion to progressive disease or death due to any reason, whichever occurred first (up to approximately 63 months)
measure: Overall Survival (OS)
timeFrame: From the date of JCAR017 infusion to the date of death due to any reason (up to approximately 63 months).
measure: Duration of Response (DOR)
timeFrame: From JCAR017 infusion until disease progression, death due to any reason, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
measure: Maximum Concentration (Cmax) of JCAR017 by qPCR
timeFrame: At baseline and up until 24 months post JCAR017 infusion
measure: Time to Peak Concentration (Tmax) of JCAR017 by qPCR
timeFrame: At baseline and up until 24 months post JCAR017 infusion
measure: Total Exposure to JCAR017 as Measured by Area Under the Curve (AUC) of JCAR017 by qPCR
timeFrame: At baseline and up until 24 months post JCAR017 infusion
measure: Percent of Participants With Presence of JCAR017 Transgene in Peripheral Blood by qPCR
timeFrame: At Day 29 and Months 2, 3, 6, 9, 12, 18, and 24 post JCAR017 infusion.
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) Scores
timeFrame: At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.
measure: Change From Baseline in Functional Assessment of Cancer Treatment-Lymphoma "Additional Concerns" Subscale (FACT-LymS) Scores
timeFrame: At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Local Institution - 101
city: Gent
country: Belgium
facility: Local Institution - 351
city: Helsinki
country: Finland
facility: Local Institution - 551
city: Lille
country: France
facility: Local Institution - 202
city: Paris Cedex 10
country: France
facility: Local Institution - 203
city: Pierre Benite cedex
country: France
facility: Local Institution - 201
city: Dresden
country: Germany
facility: Local Institution - 152
city: Heidelberg
country: Germany
facility: Local Institution - 155
city: Köln
country: Germany
facility: Local Institution - 151
city: München
country: Germany
facility: Local Institution - 154
city: Ulm
country: Germany
facility: Local Institution - 153
city: Milan
country: Italy
facility: Local Institution - 402
city: Torino
country: Italy
facility: Local Institution - 401
city: Chuo-ku
country: Japan
facility: Local Institution - 601
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 602
state: Tokyo
city: Rotterdam
country: Netherlands
facility: Local Institution - 301
city: Barcelona
country: Spain
facility: Local Institution - 451
city: Bern
country: Switzerland
facility: Local Institution - 251
city: Manchester
country: United Kingdom
facility: Local Institution - 502
state: Lancashire
city: London
country: United Kingdom
facility: Local Institution - 501
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.