This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (alloHCT).
CD33 is a preferential target for AML CAR T cell therapy due to its surface expression on the majority (\>80%) of AML blasts and due to the extensive prior clinical experience demonstrating safety and efficacy of targeting CD33 with Mylotarg (gemtuzumab ozogamicin). VCAR33 is being developed as a potential new treatment for patients with relapsed/refractory (R/R) AML after alloHCT. In this Phase 1/2 trial, the safety and efficacy of lentiviral-transduced CD33-directed CAR T cells (VCAR33) generated from the patient's prior allogeneic stem cell donor will be tested. It is hypothesized that CAR T cell production from healthy donors will not only eliminate delays in production due to lymphopenia but also reduce concerns for suboptimal T cell function from exposure to systemic immunosuppression or chemotherapeutic agents. Approximately 24 eligible patients with R/R AML after alloHCT will be enrolled in one of two separate arms based on disease burden (morphologic disease versus measurable residual disease (MRD ) positive). The maximum tolerated dose of VCAR33 will be determined using a 3+3 trial design within each arm. Dose escalation can only occur after a minimum of 3 patients have completed the dose-limiting toxicity (DLT) observation period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy
University of California San Diego Moores Cancer Center
La Jolla, California, United States
Stanford Cancer Institute
Stanford, California, United States
Incidence of dose-limiting toxicities
Time frame: Day 28
Incidence of GVHD related to VCAR33
Time frame: Up to 24 months
Percentage of patients who achieve response
Time frame: Up to 24 months
Overall survival post-VCAR33 infusion
Time frame: Up to 24 months
Progression-free survival post-VCAR33 infusion
Time frame: Up to 24 months
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