CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
|ClinicalTrials.gov Identifier: NCT01475058|
Recruitment Status : Completed
First Posted : November 21, 2011
Last Update Posted : February 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Mantle Cell Lymphoma Refractory Chronic Lymphocytic Leukemia||Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||April 2012|
|Primary Completion Date :||April 2014|
|Study Completion Date :||July 2014|
Experimental: Treatment (T cell therapy)
Patients undergo one IV infusion of donor-derived CD8+ central memory-derived CMV/CD19 or EBV/CD19 bi-specific T cells, at least 30 days after HCT.
Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV
Other Name: allogeneic CMV-specific CTLs
- Safety and toxicity assessment of study treatment [ Time Frame: Up to day 42 after the T cell infusion ]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.
- Feasibility assessment of study treatment [ Time Frame: Up to 5 years ]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.
- Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells [ Time Frame: Up to 15 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01475058
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Cameron Turtle||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|