CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
Condition: 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
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Recurrence; Philadelphia Chromosome
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
Intervention type(s): Biological
Intervention description(s): Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV
Other intervention name(s): allogeneic CMV-specific CTLs
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment