CAR T Cells in Mesothelin Expressing Cancers

Summary

Participation Requirements

Description

This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCART-meso cells with and without cyclophosphamide and via different routes of administration. Cohort 1 (N=3-6): will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced huCART-meso cells on day 0 withou...

This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCART-meso cells with and without cyclophosphamide and via different routes of administration. Cohort 1 (N=3-6): will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen. Cohort 2 (N=3-6): will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced huCART-meso cells on day 0, following a flat dose of 1 gram/m2 of cyclophosphamide administered 2-4 days prior to huCARTmeso cells (day -4 to day -2). Cohort 3 (N=3-6): will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen. **Cohort 3 permanently closed** Cohort 4 subjects (N=3-6) will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced huCART-meso cells on day 0, following a flat dose of 1 gram/m^2 of cyclophosphamide administered 2-4 days prior to huCART-meso cells (day -4 to day -2). **Cohort 4 permanently closed** Cohort 5 (N=up to 6): will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced huCART-meso cells on day 0 by intrapleural infusion (IP) through an indwelling pleural catheter without any conditioning chemotherapeutic regimen. The safety of this dose level has been established by Cohorts 1 and 2. Cohort 6 (N=up to 6): will receive lentiviral transduced huCART-meso cells at a dose of 1-3x10^7 via IV infusion on Day 0, following a flat dose of 1 gram/m^2 of cyclophosphamide administered 2-4 days prior to huCART-meso cells (~Day -4 to -2). This initial infusion may be followed by up to two additional IV infusions of huCART-meso cells at the same dose level, given between 21-42 days apart, if the subject meets eligibility to receive additional infusions. Cyclophosphamide will not be repeated prior to subsequent doses of huCART-meso cells. Enrollment into Cohort 6 will occur in parallel with Cohort 5. Cohort 7 (N = up to 6): will receive a single dose of 1-3x107 huCART-meso cells/m2 via intraperitoneal (i.p.) administration, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days by intravenous infusion. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (+/- 1 day) prior to the 1st infusion of huCART-meso cells. This initial i.p. infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart. The subject must meet eligibility to receive additional infusions . Lymphodepleting chemotherapy will not be repeated prior to additional infusions of huCART-meso cells. The Maximum Tolerated Dose (MTD) is defined as the dose at which 0-1 DLT occurs in 6 evaluable subjects tested within the dose range of this study. The maximum tolerated dose has been established as 1-3x10^7/m^2 lentiviral transduced huCART-meso cells. Adverse events will be collected and evaluated during the protocol specified adverse event reporting period

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