Phase I study to establish safety and feasibility of intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy
This is a Phase I study evaluating the safety and feasibility of intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells in 4 cohorts with or without cyclophosphamide + fludarabine in a 3+3 dose escalation design. The DLT observation period is 28 days post CAR T cell infusion. The Maximum Tolerated Dose (MTD) is defined as the dose at which 0 or 1 DLT occurs in 6 evaluable subjects tested within the dose range of this study. Cohort 1: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy. Cohort 2: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine. Cohort 3: (n=3 to 6 subjects): Single infusion of 1-3x108 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine. Cohort -1: (n= 3 to 6 subjects): Single Infusion of 1-3x106 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy. Up to 6 subjects will be infused in Cohort -1 with ≤ 1 DLT/6 subjects to establish the MTD.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.
Patients will first be pre-screened for alpha folate receptor expression. The test for alpha folate receptor expression is a laboratory developed test+, developed and conducted by the Hospital of the University of Pennsylvania Pathology and Laboratory Medicine lab to determine subject eligibility. This test is not an approved FDA device and its use is investigational.
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States
Number of Study Subjects With Treatment-related Adverse Events Using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
For this study, collection of adverse events will begin at the time of apheresis and will continue until the subject is off-study.
Time frame: Up to 34 months
Manufacturing Feasibility
Manufacturing feasibility is determined based on the "manufacturing failures" products. The number of manufactured products that do not meet release criteria for vector transduction efficiency, CART+ cell number, T cell purity, viability, and sterility will be determined and defined as "manufacturing failures".
Time frame: 8 weeks
Clinical Feasibility
Clinical feasibility is defined as the proportion of subjects enrolled on this protocol who do not receive MOv19-BBz CAR T cells. Reasons for this occurrence include rapid clinical deterioration or death, and subject withdrawal.
Time frame: 8 weeks
Progression-free Survival (PFS)
PFS will be evaluated up to 5 years post-infusion or until subjects initiate a cancer-related therapy
Time frame: Up to 33 months
Overall Response Rates (ORR)
ORR is the proportion of subjects with a best response of CR or PR based on RECIST 1.1, as compared to baseline. ORR will be evaluated up to 5 years post-infusion or until subjects initiate a cancer-related therapy.
Time frame: Up to 33 months
Overall Survival (OS)
Overall survival is defined as the time from the date of the infusion to the date of death due to any reason. OS will be evaluated up to 15 years post-infusion.
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Time frame: Up to 33 months