Overview

This trial is active, not recruiting.

Conditions 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
Treatments peripheral blood stem cell transplantation (pbsct), filgrastim, polymerase chain reaction, rituximab, genetically engineered lymphocyte therapy, laboratory biomarker analysis, plerixafor, autologous hematopoietic stem cell transplantation
Phase phase 1/phase 2
Target CD20
Sponsor City of Hope Medical Center
Collaborator National Cancer Institute (NCI)
Start date September 2011
End date August 2022
Trial size 57 participants
Trial identifier NCT01318317, 09174, NCI-2011-00344, P50CA107399

Summary

This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
peripheral blood stem cell transplantation (pbsct) PBPC transplantation
Undergo autologous PBSCT
filgrastim G-CSF
Given IV
polymerase chain reaction PCR
Correlative studies
rituximab IDEC-C2B8
Given IV
genetically engineered lymphocyte therapy
Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR)
laboratory biomarker analysis
Correlative studies
plerixafor AMD 3100
Given IV
autologous hematopoietic stem cell transplantation
Undergo autologous PBSCT

Primary Outcomes

Measure
MTD based on DLTs and defining the full toxicity profile (Phase I)
time frame: Within 28 days of T-cell infusion
Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) detection above background (Phase II)
time frame: 28 days after T cell infusion

Secondary Outcomes

Measure
Rates of engraftment and persistence
time frame: 28 days after T cell infusion
Failure to engraft
time frame: Within 21 days after T-cell infusion
Progression-free survival
time frame: Up to at least 15 years
Overall survival
time frame: Up to at least 15 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate grade B-cell NHL (e.g., diffuse B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma) - History of relapse after achieving first remission with primary therapy, or failure to achieve remission with primary therapy - Life expectancy > 16 weeks - Karnofsky performance scale (KPS) >= 70% - Negative serum pregnancy test for women of childbearing potential - Research participant has an indication to be considered for autologous stem cell transplantation Exclusion Criteria: - Fails to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study; evidence of understanding includes passing the Protocol Comprehensive Screening given by the Research Subject Advocate (RSA); a legal guardian may substitute for the research participant - Any standard contraindications to myeloablative HSCT per standard of care practices at COH - Dependence on corticosteroids - Currently enrolled in another investigational therapy protocol - Human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment - History of allogeneic HSCT or prior autologous HSCT - Active autoimmune disease requiring systemic immunosuppressive therapy - Research participant(s) who are to receive radioimmunotherapy (Zevalin-based) - based conditioning regimens - Research participant(s) with known active hepatitis B or C infection

Additional Information

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
Principal investigator Leslie Popplewell
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by City of Hope Medical Center.