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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02706405
Other study ID # 9457
Secondary ID NCI-2015-0228694
Status Terminated
Phase Phase 1
First received
Last updated
Start date November 15, 2016
Est. completion date May 28, 2021

Study information

Verified date August 2022
Source Fred Hutchinson Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Drug:
Cyclophosphamide
Given IV
Biological:
Durvalumab
Given IV
Drug:
Fludarabine
Given IV

Locations

Country Name City State
United States Fred Hutch/University of Washington Cancer Consortium Seattle Washington

Sponsors (5)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Center AstraZeneca, Juno Therapeutics, Inc., MedImmune LLC, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other B-cell Depletion in Circulation, Profile of Soluble Circulating Proteins Such as Cytokines and Chemokines, and Changes in the Level of Detectable Soluble PD-L1 Up to 12 months
Other Change in the Phenotype of Tumor Cells (e.g., Expression of PD-L1) and of the Tumor Microenvironment (e.g., Infiltration by Chimeric Antigen Receptor [CAR] T Cells) Flow cytometry may be used in the blood, bone marrow, and cerebrospinal fluid (CSF) (if applicable). Baseline up to 12 months
Other Phenotype and/or Genetic Profile of Endogenous Immune Cells and CAR T Cells Flow cytometry may be used in the blood, bone marrow, and CSF (if applicable). Up to 12 months
Other Cmax of Durvalumab in Serum Up to 12 months
Other AUC of Durvalumab in Serum Up to 12 months
Other Clearance of Durvalumab in Serum Up to 12 months
Other Terminal Half-life of Durvalumab in Serum Up to 12 months
Other Antibodies and Cellular Immune Responses to JCAR014 Cellular immune responses to JCAR014 will be considered in patients who have two consecutive negative assays for JCAR014 or who have recovered endogenous B cells. Cellular responses to JCAR014 will be evaluated by assessing reactivity of patient peripheral T cells to JCAR014. Peripheral blood will be collected for these studies. Up to 12 months
Other Anti-drug Antibodies Directed Against Durvalumab Will be assessed using a validated immunoassay in serum samples. Up to 12 months
Primary Count of Participants Who Experienced Adverse Events Toxicity graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. 28 days post last infusion of Durvalumab, up to 1 year
Primary Dose Limiting Toxicity (DLT) Rates Will be summarized based on the dose limiting toxicity evaluable analysis set. The target toxicity rate for the maximum tolerated dose is 30%. Outcome will be reported as a count of patients in each arm that experienced a DLT. 28 days post first infusion of Durvalumab (for participants in Group 1) or 28 days post infusion of JCAR (for participants in Group 2)
Primary Highest Treatment Dose Administered on Study Reporting outcome as the maximum durvalumab dose that we reached on the study. Patients were monitored for 28 days post infusion for dose limiting toxicities. The DLT rate was used to determine dose escalation. The study was terminated prior to reaching the maximum tolerated dose. 28 days
Primary Maximum JCAR014 Cmax by Flow Cytometry Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. Up to 12 months
Primary Area Under the Curve (AUC) of JCAR014 by Flow Cytometry Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28. The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. Up to 28 days
Primary Maximum JCAR014 Cmax in Blood by Quantitative Polymerase Chain Reaction (qPCR) Analysis The number of copies of the CAR transgene/µg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1? sequence, with a lower limit of detection of 10 transgene copies/µg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. Up to 12 months
Primary AUC of JCAR014 Cells by qPCR Analysis The number of copies of the CAR transgene/µg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1? sequence, with a lower limit of detection of 10 transgene copies/µg of DNA. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28.The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. Up to 28 days
Primary Time to Loss of JCAR014 Detection in Blood by qPCR Analysis The number of copies of the CAR transgene/µg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1? sequence, with a lower limit of detection of 10 transgene copies/µg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. Up to 12 months, +/- 30 days
Secondary Rate of Complete Response (CR) by Investigator Assessment Using Lugano Criteria This outcome is a count of participants who experienced a best response of complete response (CR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. Up to 1 year
Secondary Rate of Partial Response (PR) by Investigator Assessment Using Lugano Criteria This outcome is a count of participants who experienced a best response of partial response (PR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. Up to 1 year
Secondary Objective Response Rate by Investigator Assessment Using Lugano Criteria ORR, defined as a count of participant with a best response of either complete response or partial response. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. Up to 1 year
Secondary Duration of Response Duration of response will be an average amount of days from first response assessment until progression or death for treated patients. Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. From first response to progressive disease or death, assessed up to 1 year
Secondary Progression Free Survival Outcome will be reported as a count of those who did not progress and did not die while on study. From date of first study treatment to progressive disease or death, assessed up to 1 year
Secondary Overall Survival Outcome will be reported as a count of participants who survived while on study. Survival was assessed up to 1 year. From date of first study treatment to death, assessed up to 1 year
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