Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title: Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor

Status Completed

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of laboratory treated T cells to see how well they work in treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia that have come back or have not responded to treatment. T cells that are treated in the laboratory before being given back to the patient may make the body build an immune response to kill cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded autologous CD8 positive (+) and CD4+ CD19 chimeric antigen receptor (CAR)-T cells for patients with advanced CD19+ B cell malignancies.

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.

II. To determine if adoptively transferred T cells traffic to the bone marrow and function in vivo.

III. To determine if the adoptive transfer of CD19 CAR-T cells results in depletion of CD19+ B cells in vivo as a surrogate for functional activity.

IV. To determine if the adoptive transfer of CD19 CAR-T cells has antitumor activity in patients with measurable tumor burden prior to T cell transfer.

V. To determine if the adoptive transfer of CD19 CAR-T cells is associated with tumor lysis syndrome.

OUTLINE: This is a phase I, dose-escalation study of autologous CD19 CAR T-cells followed by a phase II study.

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells intravenously (IV) over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity.

DOSE DENSE EXPANSION COHORT: An additional cohort will receive a second anti-CD19-CAR lentiviral vector-transduced autologous T cell infusion without additional lymphodepleting chemotherapy 10-21 days after the first infusion if adequate CD19 CAR-T cells can be produced and appropriate criteria are met.

After completion of study treatment, patients are followed up for at least 15 years. ;

Related Conditions & MeSH terms

• CD19-Positive Neoplastic Cells Present
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Non-Hodgkin Lymphoma
• Recurrent Small Lymphocytic Lymphoma
• Refractory Acute Lymphoblastic Leukemia
• Refractory Chronic Lymphocytic Leukemia
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Mantle Cell Lymphoma
• Refractory Non-Hodgkin Lymphoma
• Refractory Small Lymphocytic Lymphoma

• NCT number: NCT01865617
• Study type: Interventional
• Source: Fred Hutchinson Cancer Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 22, 2013
• Completion date: March 26, 2021