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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
204
Given IV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy
Death within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy will be assessed.
Time frame: Within 8 weeks of the study cell infusion
Dose Limiting Toxicities
Outcome will be reported as a count of participants that experienced a dose limiting toxicity on the study within 30 days post infusion.
Time frame: 30 days
Objective Response Rate of Complete Response and Partial Response
Outcome will be reported as the count of patients per arm that experienced a complete response/partial response. Complete response (CR): CR per Lugano criteria for nodal disease and minimal residual disease (MRD)-negative CR by flow cytometry for marrow disease. Partial response (PR): \> 50% reduction of the sum of the products of the perpendicular diameters of marker lesions, no progression of any existing lesions, and no new lesions.
Time frame: Up to 1 year
Overall Survival
Outcome will be reported as a count of patients who survived up to 1 year post infusion.
Time frame: Up to 1 year
Progression Free Survival
Outcome will be reported as the count of patients per arm that survived and whose disease did not progress in the 1 year timeframe post infusion.
Time frame: Up to 1 year
Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells
Duration of persistence of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients alive after 1 year and count of patients with CAR-T cells detected at 1 year.
Time frame: Up to day 365
Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells
Migration of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients with bone marrow disease involvement and count of patients with CAR-T cells detected in bone marrow at restaging.
Time frame: Up to 1 year
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