Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
Condition: Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Lymphoma
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be
      infused back to patients with B cell malignancies, including lymphoma and leukemia. The
      patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse
      events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.

      Objectives:

      To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for
      patients with B cell malignancies.

      Eligibility:

      Patients between 1 and 80 years of age, who have relapsed or refractory CD19-expressing
      B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.

      Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria
      are eligible to participate.

      Patients must have adequate organ functions.

      Design:

      Peripheral blood from patients will be collected for isolation of peripheral blood
      mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector
      encoding anti-CD19 CAR containing a CD28 or 4-1BB and a CD3 zeta as costimulatory domains.

      Patients will receive a lymphodepleting preconditioning regimen to prepare their immune
      system to accept modified T cells.

      Patients will receive an infusion of their own modified T cells. They will remain in the
      hospital to be monitored for adverse events until they have recovered from the treatment.

      Patients will have frequent follow-up visits to monitor the persistence of modified T cells
      and efficacy of the treatment.
    

Detailed description: 
      Despite progress has been made to date in the treatment of patients with B cell malignancies,
      including leukemia and lymphoma, many patients with relapsed or refractory diseases do not
      respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells
      may be an effective approach to treat the relapsed or refractory diseases. The procedure
      involves collecting PBMCs from the patients and modifying the T cells to attack the malignant
      B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric
      antigen receptor (CAR) containing the signaling domains of CD28 or 4-1BB and CD3-zeta will be
      infused back to patients with B cell malignancies, including lymphoma and leukemia. The
      patients will be pretreated with a lymphodepleting preconditioning regimen before the
      infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of
      anti-CD19 CAR-transduced T cells and the treatment efficacy.

      OBJECTIVES:

      Primary objectives:

      To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T
      cells in patients with CD19+ B-cell malignancies.

      Secondary objectives:

      To determine if the treatment regimen can result in clinical regression of B-cell
      malignancies in the patients as described above.

      To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells.
    

Intervention name(s): Drugs and Anti-CD19-CAR transduced T cells
Intervention type(s): Combination Product
Intervention description(s): Drug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 IV will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Biological: Anti-CD19-CAR transduced T cells Modified cells will be infused IV over 30 minutes (1-3 days after the last dose of fludarabine).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment