Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT01318317|
Recruitment Status : Active, not recruiting
First Posted : March 18, 2011
Last Update Posted : September 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma||Procedure: peripheral blood stem cell transplantation (PBSCT) Biological: filgrastim Genetic: polymerase chain reaction Biological: rituximab Biological: genetically engineered lymphocyte therapy Other: laboratory biomarker analysis Drug: plerixafor Procedure: autologous hematopoietic stem cell transplantation||Phase 1 Phase 2|
PRIMARY OBJECTIVES: I. To assess the safety of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (TCM)-enriched cluster of differentiation (CD)8+ T cells genetically-modified to express a CD19-specific chimeric antigen receptor (CAR) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplantation (aHSCT) for research participants with high-risk intermediate grade B-lineage non-Hodgkin lymphomas who have relapsed after primary therapy, or who did not achieve complete remission with primary therapy. (Phase I)
II. To determine the maximum tolerated dose (MTD) on dose limiting toxicities (DLTs) and to describe the full toxicity profile. (Phase I)
III. To determine the rate of research participants receiving TCM-enriched CD8+ T cells genetically-modified to express a CD19-specific CAR for which the transferred cells are detected in the circulation 28 days (+/- 3 days) by woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) quantitative (Q)-polymerase chain reaction (PCR). (Phase II)
SECONDARY OBJECTIVES: I. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell product as it relates to the number of cells infused. (Phase II)
II. To study the impact of this therapeutic intervention on the development of CD19+ B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred CD19-specific T cells. (Phase II)
III. To describe the progression-free and overall survival of treated research participants on this protocol. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of genetically engineered lymphocyte therapy followed by a phase II study. Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with filgrastim and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.
After completion of study treatment, patients are followed up periodically for at least 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Cellular Immunotherapy Using Central Memory-Enriched CD8+ T Cells Lentivirally Transduced to Express A CD19-Specific Chimeric Immunoreceptor Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma|
|Actual Study Start Date :||October 20, 2011|
|Estimated Primary Completion Date :||August 2022|
|Estimated Study Completion Date :||August 2022|
Experimental: Treatment (cellular adoptive immunotherapy following PBSCT)
Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
Procedure: peripheral blood stem cell transplantation (PBSCT)
Undergo autologous PBSCT
Genetic: polymerase chain reaction
Other Name: PCR
Biological: genetically engineered lymphocyte therapy
Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR)
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSCT
- MTD based on DLTs and defining the full toxicity profile (Phase I) [ Time Frame: Within 28 days of T-cell infusion ]Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity. Determination of the full toxicity profile will include analyses of adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) detection above background (Phase II) [ Time Frame: 28 days after T cell infusion ]
- Rates of engraftment and persistence [ Time Frame: 28 days after T cell infusion ]Rates and associated 95% confidence intervals will be estimated.
- Failure to engraft [ Time Frame: Within 21 days after T-cell infusion ]Rates and associated 95% confidence intervals will be estimated.
- Progression-free survival [ Time Frame: Up to at least 15 years ]Estimated using the Kaplan-Meier methods.
- Overall survival [ Time Frame: Up to at least 15 years ]Estimated using the Kaplan-Meier methods.
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): NCT01318317
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||Leslie Popplewell||City of Hope Medical Center|