A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-Derived Virus-Specific CD8+ T-Cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
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)
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.
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Up to day 42 after the T cell infusion
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|