Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03338972|
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : May 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143 Drug: Cyclophosphamide Drug: Fludarabine Other: Laboratory Biomarker Analysis Procedure: Leukapheresis||Phase 1|
I. To evaluate the safety of adoptive therapy with ex vivo expanded autologous CD8+ plus CD4+ T cells transduced to express a human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) for patients with relapsed or treatment refractory multiple myeloma.
I. To determine the duration of in vivo persistence and the phenotype of long lived CAR-T cells.
II. To determine the degree to which adoptively transferred T cells traffic to multiple myeloma (MM) cells in the bone marrow (BM) and function in vivo.
III. To estimate the antitumor activity of adoptively transferred BCMA-specific CAR-expressing T lymphocytes (BCMA CAR-T cells).
OUTLINE: This is a dose-escalation study of BCMA-specific CAR-expressing T lymphocytes.
Patients undergo leukapheresis to obtain their immune cells, from which CAR-T cells are produced. A few weeks later, patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning 36-96 hours after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes intravenously (IV) over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).
After completion of study treatment, patients are followed up at 60, 90, 120, 180, and 365 days and then annually up to 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Adoptive Immunotherapy for Advanced B-Cell Maturation Antigen (BCMA)+ Multiple Myeloma With Autologous CD4+ and CD8+ T Cells Engineered to Express a BCMA-Specific Chimeric Antigen Receptor|
|Actual Study Start Date :||November 29, 2017|
|Estimated Primary Completion Date :||December 15, 2020|
|Estimated Study Completion Date :||December 15, 2022|
Experimental: Treatment (chemotherapy, BCMA CAR-T cells)
Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).
Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143
Other Name: Fluradosa
Other: Laboratory Biomarker Analysis
- Dose-limiting toxicity (DLT) [ Time Frame: Up to 28 days after T cell infusion ]Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Final DLT rates at each dose level will be estimated by the Continual Reassessment Method (CRM) algorithm.
- Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 42 days after T cell infusion ]All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.
- Duration of persistence of adoptively transferred BCMA CAR-T cells [ Time Frame: Baseline up to 15 years ]
- Migration of adoptively transferred BCMA CAR-T cells [ Time Frame: Baseline up to 15 years ]
- Objective response rate (ORR) [ Time Frame: Baseline up to 3 months after T cell infusion ]Proportion of patients with a best response of either complete response or partial response, assessed using modified International Myeloma Working group response criteria.
- Progression-free survival (PFS) [ Time Frame: Assessed up to 15 years ]Assessed using modified International Myeloma Working Group response criteria
- Overall survival (OS) [ Time Frame: Assessed up to 15 years ]
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): NCT03338972
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Immunotherapy Trials Intake, SCCA 206-606-4668 firstname.lastname@example.org|
|Principal Investigator: Damian J. Green|
|Principal Investigator:||Damian Green||Fred Hutch/University of Washington Cancer Consortium|