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RATIONALE: Using T cells from the patient that have been treated in the laboratory may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated T cells together with cyclophosphamide may kill more cancer cells.
PURPOSE: This is a two-stage protocol, consisting of a single-institution phase I safety study and multi-institution phase IIa extension study.
Full description
OBJECTIVES:
Phase 1: The primary objective is to assess the safety of autologous T cells genetically modified to express chimeric antigen receptor (CAR) targeting CD19 antigen (19-28z) with or without conditioning chemotherapy.
• Phase IIa: The primary objective is to compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 (19-28z) and 4-1BB (CART-19:CD3z-4-1BB) in the CAR construct.
To compare the in vivo survival of genetically modified 19-28z CAR+ T cells after T cell infusion alone or in combination with conditioning chemotherapy.
OUTLINE:
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy. In Step 1, a cohort of patients will receive the lowest planned dose of 19-28z+ modified T cells. In Step 2, a cohort of patients will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of patients in the cohort (Step 2) experience unanticipated dose-limiting toxicity. In Step 3, a cohort of patients will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of patients in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be be expanded to include up to 15 patients. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) patients will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells. However, to maximize safety for WM patients, they will be treated at the lower dose of modified T cells (1x106 19-28z+ T cells/kg). If no toxicity is observed in the initial cohort, the dose may be increased in a standard 3-step dose-escalation scheme as described above.
In the Phase IIa extension part of the trial, 12 patients from MSKCC will be enrolled, and will be treated with co-infusion of 19-28z and CART-19:CD3z-4-1BB+ modified T cells mixed at 1:1 ratio at the MTD of T cells determined from the phase I trial.
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Inclusion and exclusion criteria
Inclusion:
• Patients must have the following CD19+ B cell leukemia or lymphoma either with relapsed or chemotherapy-refractory disease or with evidence of residual disease following therapy.
In all cases, patient's disease must be confirmed at MSKCC.
Exclusion:
Primary purpose
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50 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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