Ignite Creation Date:
2025-12-25 @ 3:24 AM
Ignite Modification Date:
2026-02-21 @ 8:26 AM
Study NCT ID:
NCT02706405
Status:
TERMINATED
Last Update Posted:
2022-08-24
First Post:
2016-02-24
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Study Overview
Official Title:
A Phase 1b Study of JCAR014, Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor, in Combination With Durvalumab (MEDI4736) for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Status:
TERMINATED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated due to slow accrual.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial studies whether anti-CD19-chimeric antigen receptor (CAR) lentiviral vector-transduced autologous T cells (JCAR014) and durvalumab are safe in combination and can work together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). JCAR014 is made of each patient's immune cells (T cells) that have a new gene added to them in a laboratory, which programs them to kill lymphoma cells. Durvalumab is a type of drug called a monoclonal antibody, targeted to PD-L1 that may help immune cells attack cancer cells more effectively and thus help JCAR014 work better.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the safety of JCAR014 in combination with durvalumab in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).
II. To determine the maximum tolerated dose (MTD) of durvalumab in combination with JCAR014.
III. To characterize the pharmacokinetic (PK) profile of JCAR014.
SECONDARY OBJECTIVES:
I. To assess the antitumor activity of JCAR014 in combination with durvalumab in R/R B-cell NHL.
II. To estimate the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients treated with JCAR014 in combination with durvalumab.
III. To characterize the PK profile of durvalumab. IV. To assess the immunogenicity of JCAR014 and durvalumab.
EXPLORATORY OBJECTIVE:
I. To assess the pharmacodynamic effects of JCAR014 and durvalumab in blood and within the tumor.
OUTLINE: This is a dose-escalation study of durvalumab administered with a single fixed dose of JCAR014. Patients are assigned to 1 of 2 treatment arms, listed as Groups 1 and 2 below.
LYMPHODEPLETING CHEMOTHERAPY: All patients receive cyclophosphamide and fludarabine intravenously (IV) for 3 days starting approximately on day -5 or day -4.
GROUP I: Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 30 days for 30 months, every 3 months for 12 months, then periodically for at least 15 years.
I. To evaluate the safety of JCAR014 in combination with durvalumab in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).
II. To determine the maximum tolerated dose (MTD) of durvalumab in combination with JCAR014.
III. To characterize the pharmacokinetic (PK) profile of JCAR014.
SECONDARY OBJECTIVES:
I. To assess the antitumor activity of JCAR014 in combination with durvalumab in R/R B-cell NHL.
II. To estimate the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients treated with JCAR014 in combination with durvalumab.
III. To characterize the PK profile of durvalumab. IV. To assess the immunogenicity of JCAR014 and durvalumab.
EXPLORATORY OBJECTIVE:
I. To assess the pharmacodynamic effects of JCAR014 and durvalumab in blood and within the tumor.
OUTLINE: This is a dose-escalation study of durvalumab administered with a single fixed dose of JCAR014. Patients are assigned to 1 of 2 treatment arms, listed as Groups 1 and 2 below.
LYMPHODEPLETING CHEMOTHERAPY: All patients receive cyclophosphamide and fludarabine intravenously (IV) for 3 days starting approximately on day -5 or day -4.
GROUP I: Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 30 days for 30 months, every 3 months for 12 months, then periodically for at least 15 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2015-02286 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 9457 | OTHER | Fred Hutch/University of Washington Cancer Consortium | View | |
| P30CA015704 | NIH | None | https://reporter.nih.gov/quic… | View |
| R01CA136551 | NIH | None | https://reporter.nih.gov/quic… | View |
| RG6616001 | OTHER | Fred Hutch/University of Washington Cancer Consortium | View |