This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.
PRIMARY OBJECTIVES: I. To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A) II. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B) SECONDARY OBJECTIVES: I. To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells. II. To determine if adoptively transferred bi-specific CD8+ T cells traffic to the bone marrow and function in vivo. III. To determine if adoptively transferred bi-specific CD8+ T cells proliferate in allogeneic HCT recipients that reactivate CMV or EBV. IV. To determine if the adoptive transfer of bi-specific CD8+ T cells eliminates CD19+ tumor cells in the subset of patients with a measurable tumor burden prior to T cell transfer. OUTLINE: At least 30 days after HCT, patients will receive one intravenous (IV) infusion of CMV/CD19 or EBV/CD19 bi-specific CD8+ T cells. After completion of study treatment, patients are followed up periodically for 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Safety and toxicity assessment of study treatment
Incidence of grade \>= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.
Time frame: Up to day 42 after the T cell infusion
Feasibility assessment of study treatment
If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.
Time frame: Up to 5 years
Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells
Time frame: Up to 15 years
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