A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With Relapsed/Refractory B-cell Malignancies (PLATFORM) (PLATFORM)
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|ClinicalTrials.gov Identifier: NCT03310619|
Recruitment Status : Recruiting
First Posted : October 16, 2017
Last Update Posted : June 13, 2018
This is an open-label, multi-arm, multi-cohort, multi-center, Phase 1/2 study to determine the safety, tolerability, PK, efficacy and patient reported quality of life of JCAR017 in combination with various agents. The first combination, defined as Arm A, will evaluate JCAR017 in combination with durvalumab. Within each arm, cohorts and subcohorts will test different doses and schedules of the combination agent(s).
The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2).
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma, Non-Hodgkin Lymphoma, Large B-Cell, Diffuse Lymphoma, Follicular||Biological: JCAR017 Drug: Durvalumab||Phase 1 Phase 2|
This is a global, open-label, multi-arm, multi-cohort, multi-center, Phase 1/2 study to determine the safety, tolerability, PK, efficacy and patient reported quality of life of JCAR017 in combination with various agents. This protocol is intended to evaluate various drug combinations with JCAR017, as separate arms, over the life of the protocol, using the same objectives.
During the Phase 1 part, different arms may be opened to test JCAR017 in combination with combination agent(s). Within each arm, different doses and schedules of JCAR017 and the combination agent(s) may be tested in several cohorts and subcohorts per arm. During the Phase 2 part of the study, the expansion of any dose level and schedule that has been shown to be safe may occur.
Arm A will test JCAR017 in combination with durvalumab in adult subjects with R/R aggressive B-cell NHL.
All subjects from Phase 1 and Phase 2 will be followed for 24 months following JCAR017 infusion. Post-study follow-up for survival, relapse, long-term toxicity (including new malignancies), and viral vector safety will continue under a separate long-term follow-up (LTFU) protocol for up to 15 years after the JCAR017 dose as per health authority regulatory guidelines.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Exploratory Phase 1/2 Trial To Evaluate The Safety And Efficacy Of JCAR017 Combinations In Subjects With Relapsed/Refractory B-Cell Malignancies (PLATFORM)|
|Actual Study Start Date :||November 28, 2017|
|Estimated Primary Completion Date :||March 30, 2021|
|Estimated Study Completion Date :||March 30, 2021|
Experimental: JCAR017 in combination with Durvalumab
JCAR017 will be administered at a single flat dose of 5 x 10^7 CAR+T cells or 1 x 10^8 CAR+T cells. The combination agent will be administered at different doses and/ or schedules.
Gene modified autologous T cells
Other Name: MEDI4736
- Dose-limiting toxicity (DLT) rates [ Time Frame: From first dose of the combination agent until 1 month (28 days) after JCAR017 infusion or from JCAR017 infusion until 1 month (28 days) after the first dose of combination agent ]Percentage of participants experiencing DLTs
- Complete Response Rate [ Time Frame: Up to approximately 6 months post-JCAR017 infusion ]Is defined as the proportion of subjects achieving a CR according to the Lugano Classification.
- Adverse Events (AEs) [ Time Frame: Up to approximately 24 months ]Number of participants with adverse events, type of adverse events, severity of adverse events, and number of participants with laboratory abnormalities, type of laboratory abnormalities and severity of laboratory abnormalities.
- Progression-free survival (PFS) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Time from start of JCAR017, or start of combination agent, whichever occurs first, to progressive disease (PD) or death from any cause
- Overall survival (OS) [ Time Frame: Up to approximately 3.5 years ]Time from start of JCAR017, or start of combination agent, whichever occurs first, to death due to any cause
- Overall response rate (ORR) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Percentage of subjects achieving an objective response of partial response (PR) or better according to the Lugano Classification
- Duration of response (DOR) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Time from first response to disease progression or death from any cause
- Event-free survival (EFS) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Time from start of JCAR017, or start of combination agent, whichever occurs first, to death from any cause, disease progression, or starting a new antilymphoma therapy whichever occurs first
- Pharmacokinetic (PK)- Cmax [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Maximum observed concentration in plasma
- Pharmacokinetic (PK)- Tmax [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Time to maximum concentration
- Pharmacokinetic (PK)- AUC [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Area under the plasma concentration vs time curve
- Health-related quality of life (HRQoL) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]Is described as parameters assessed by European Organization for Research and Treatment of Cancer
- Quality of Life C30 questionnaire (EORTC-QLQ-C30) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]EORTC-QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.
- European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) [ Time Frame: Up to approximately 24 months post-JCAR017 infusion ]The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03310619
|Contact: Associate Director Clinical Trial Disclosurefirstname.lastname@example.org|
|United States, California|
|City of Hope National Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|United States, Illinois|
|Northwestern University School of Medicine||Recruiting|
|Chicago, Illinois, United States, 60611-5975|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|United States, Nebraska|
|University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198-7680|
|United States, Pennsylvania|
|University of Pennsylvania||Not yet recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Study Director:||Jens Hasskarl, PD Dr. med||Celgene|