Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma
NCT ID: NCT01318317
Last Updated: 2025-04-25
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
8 participants
INTERVENTIONAL
2011-09-19
2026-02-26
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (cellular adoptive immunotherapy following PBSCT)
Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with G-CSF and/or plerixafor. Some patients may also receive rituximab 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.
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSCT
Filgrastim
Given IV
Genetically Engineered Lymphocyte Therapy
Receive ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR
Laboratory Biomarker Analysis
Correlative studies
Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSCT
Plerixafor
Given IV
Rituximab
Given IV
Interventions
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Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSCT
Filgrastim
Given IV
Genetically Engineered Lymphocyte Therapy
Receive ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR
Laboratory Biomarker Analysis
Correlative studies
Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSCT
Plerixafor
Given IV
Rituximab
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
City of Hope Medical Center
OTHER
Responsible Party
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Principal Investigators
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Elizabeth L Budde, MD,PhD
Role: PRINCIPAL_INVESTIGATOR
City of Hope Medical Center
Locations
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City of Hope Medical Center
Duarte, California, United States
Countries
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References
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Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, Norris AP, Wong CW, Urak RZ, Chang WC, Khaled SK, Siddiqi T, Budde LE, Xu J, Chang B, Gidwaney N, Thomas SH, Cooper LJ, Riddell SR, Brown CE, Jensen MC, Forman SJ. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980-90. doi: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2011-00344
Identifier Type: REGISTRY
Identifier Source: secondary_id
09174
Identifier Type: OTHER
Identifier Source: secondary_id
09174
Identifier Type: -
Identifier Source: org_study_id
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