CAR T Cells in Mesothelin Expressing Cancers
- Conditions
- Peritoneal CarcinomaMesotheliomas PleuralLung AdenocarcinomaOvarian CancerFallopian Tube CancerMesothelioma Peritoneum
- Interventions
- Biological: huCART-meso cells
- Registration Number
- NCT03054298
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
Phase I study to establish safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells with or without lymphodepletion.
- Detailed Description
This is a Phase I study evaluating the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells with and without lymphodepleting chemotherapy.
* Cohort 1 (N=3-6): will receive a single dose of 1-3x10\^7 huCARTmeso cells/m\^2 on day 0 without any conditioning chemotherapeutic regimen.
* Cohort 2 (N=3-6): will receive a single dose of 1-3x10\^7 huCARTmeso cells/m\^2 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 huCARTmeso cells/m\^2 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 a dose of 1-3x10\^7 huCARTmeso cells/m\^2 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 1-3x10\^7 huCART-meso cells/m\^2 via intraperitoneal (i.p.) administration, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/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 huCARTmeso cells/m\^2.
Adverse events will be collected and evaluated during the protocol specified adverse event reporting period
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 huCART-meso cells Single dose of 1-3x10\^7 huCARTmeso cells/m\^2 Cohort 4 huCART-meso cells PERMANENTLY CLOSED Cohort 5 huCART-meso cells Single dose of 1-3x10\^7 huCART-meso cells/m\^2 day 0 by intrapleural infusion (IP) through an indwelling pleural catheter without any conditioning chemotherapeutic regimen. Cohort 6 huCART-meso cells Cyclophosphamide 1 gram/m\^2 administered 2-4 days prior to dose of 1-3x10\^7 huCART-meso cells/m\^2 via IV infusion on Day 0. This initial infusion may be followed by up to two additional IV infusions of huCART-meso cells at the same dose level, given approximately 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. Cohort 3 huCART-meso cells PERMANENTLY CLOSED Cohort 7 huCART-meso cells Cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day given over 3 days by IV infusion followed by a single dose of 1-3x10\^7 huCART-meso cells/m\^2 via intraperitoneal (i.p.) administration. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (+/- 1 day) prior to the 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. Cohort 2 huCART-meso cells Cyclophosphamide 1 gram/m\^2 administered 2-4 days prior to a single dose of 1-3x10\^7 huCARTmeso cells/m\^2
- Primary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 2 years
- Secondary Outcome Measures
Name Time Method Progression-free survival Year 2 Objective response rate Year 2 Overall survival 15 years
Trial Locations
- Locations (1)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States