A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
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|ClinicalTrials.gov Identifier: NCT03277729|
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : October 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|CD20 Positive Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Lymphoplasmacytic Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Lymphoplasmacytic Lymphoma Refractory Mantle Cell Lymphoma Refractory Transformed Non-Hodgkin Lymphoma Recurrent Transformed B-cell Non-Hodgkin Lymphoma Recurrent Transformed Chronic Lymphocytic Leukemia Refractory Marginal Zone Lymphoma Refractory Transformed B-cell Non-Hodgkin Lymphoma Refractory Transformed Chronic Lymphocytic Leukemia||Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Other: Laboratory Biomarker Analysis Procedure: Leukapheresis Drug: Fludarabine Phosphate||Phase 1 Phase 2|
I. To estimate the maximum tolerated dose (MTD) of adoptive cellular immunotherapy using ex vivo transduced and expanded autologous T cells expressing a third (3rd)-generation fully human CD20-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma (B-NHL).
I. To evaluate the safety and toxicity associated with CD20 CAR T cell infusions.
II. To evaluate preliminary antitumor activity of adoptively transferred T cells in patients with measurable tumor burden prior to treatment as measured by overall response rate (ORR) and complete remission (CR) rate.
III. To evaluate progression-free survival (PFS) and overall survival (OS) among patients treated with adoptively transferred CD20-specific T cells.
OUTLINE: This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy.
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide intravenously (IV). Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion.
Patients will be actively participating in the study for approximately 15 months. The total time includes the time for the T cells to be made, the T cell infusion, and for approximately 12 months after the T cell infusion is given. After completion of study treatment, patients are followed up for a minimum of 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas|
|Actual Study Start Date :||December 5, 2017|
|Estimated Primary Completion Date :||November 16, 2022|
|Estimated Study Completion Date :||November 16, 2037|
Experimental: Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion.
Biological: Chimeric Antigen Receptor T-Cell Therapy
Given CD20 CAR T cell IV
Other Name: Fluradosa
Other: Laboratory Biomarker Analysis
Drug: Fludarabine Phosphate
- Dose-limiting toxicity [ Time Frame: Up to 28 days ]Will be graded by Common Terminology Criteria for Adverse Events version 4.0.
- Complete remission [ Time Frame: Up to 15 years ]Will be assessed based on the Lugano criteria.
- Progression-free survival (PFS) [ Time Frame: Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years ]A Cox proportional hazards model will be used to evaluate PFS.
- Overall survival (OS) [ Time Frame: Duration from study enrollment to death due to any cause, assessed up to 15 years ]A Cox proportional hazards model will be used to evaluate OS.
- Incidence of adverse events [ Time Frame: Up to 15 years ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
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): NCT03277729
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Mazyar Shadman 206-667-5467 firstname.lastname@example.org|
|Principal Investigator: Mazyar Shadman|
|Principal Investigator:||Mazyar Shadman||Fred Hutch/University of Washington Cancer Consortium|