NCT01475058

CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• 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

Interventions

Type	Name	Description
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

Timeline

• Start date: 2012-04-01
• Primary completion: 2014-04-01
• Completion: 2014-07-01
• First posted: 2011-11-21
• Last updated: 2017-02-15

Locations

1 site across 1 country: United States