This is a Phase 1 interventional, single-arm, open- label, treatment study designed to evaluate the safety of h20.19 CAR T cells in patients with B-cell malignancies that have failed prior therapies.
The purpose of this study is to determine the safety of fully human lentiviral 20.19 (h20.19) CAR T cells in patients with relapsed, refractory B-cell malignancies. A maximum of 12 patients will be treated in the Phase 1 cohort followed by a 12-patient expansion cohort (approximately 21 to 24 patients total).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Dose escalation: CAR-T cells will be administered at one of two dose levels either fresh or thawed after cryopreservation by IV injection.
Dose escalation: CAR-T cells will be administered at one of two dose levels either fresh or thawed after cryopreservation by IV injection.
Dose expansion: The maximum tolerated dose intervention will be updated when it is determined. It will be one of two doses: 1 X 10\^6 cells/kg or 2.5 X 10\^6 cells/kg.
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Maximum tolerated dose
The maximum tolerated dose (MTD) is the highest dose of a drug or treatment that does not cause dose-limiting toxicities (DLTs). This trial will utilize a 3+3 design to determine the safe dose. Three patients are enrolled and treated at the starting (lowest) dose level. * 0 DLTs: If none of the three patients experience a DLT, the next cohort of three patients is treated at the next higher dose level. * 1 DLT: If one patient experiences a DLT, an additional three patients are enrolled at the same dose level (expanding the cohort to six patients total). * 2 or more DLTs: If two or more patients in a cohort of three (or two or more in an expanded cohort of six) experience DLTs, the MTD is considered to have been exceeded. The trial stops escalating and the previous dose level is defined as the MTD.
Time frame: 28 days post CAR-T cell infusion
Adverse Events
The number of subjects with adverse events, defined as non-hematologic Grade 3/4 events per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, as well as Grade 3-4 CRS, ICANS, and IEC-HS events per the recent ASTCT consensus criteria, that are possibly, probably, or definitely related to study treatment and do not resolve to ≤ Grade 2 by Day 28 post-infusion.
Time frame: Up to 2 Years post CAR-T cell infusion
Overall Response Rate (ORR)
ORR is defined as the number of subjects who achieve a best overall response of complete response (CR) or partial response (PR), as determined by the Lugano (for Non-Hodgkin Lymphoma subjects) or Hallek (for Chronic Lymphocytic Leukemia subjects) criteria, following h20.19 CAR T-cell infusion.
Time frame: 28 days post CAR-T cell infusion
Complete Response (CR) Rate
CR rate is defined as the number of subjects who achieve a CR following h20.19 CAR T-cell infusion.
Time frame: 28 days post CAR-T cell infusion
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Duration of Response (DOR)
DOR is defined as the time from the first documented CR or partial response (PR) following h20.19 CAR T-cell infusion to disease progression, as determined by the Lugano or Hallek criteria, or death, whichever occurs first.
Time frame: Up to 2 years post CAR-T cell infusion
Relapse rate
Relapse rate is defined as the number of subjects who experience relapse among those who achieve a best overall response rate of CR or PR following h20.19 CAR T-cell infusion.
Time frame: 120 days; 1 year; 2 year post CAR-T cell infusion
Overall Survival (OS)
OS is defined as the time from h20.19 CAR T-cell infusion to documented death.
Time frame: 120 days; 1 year; 2 year post CAR-T cell infusion
Progression-free Survival (PFS)
PFS is defined as the time from h20.19 CAR T-cell infusion to documented disease progression or death, whichever occurs first.
Time frame: 120 days; 1 year; 2 year post CAR-T cell infusion