Phase 1, Open Label, Dose Escalation Study to Evaluate the Safety, Expansion, Persistence, and Preliminary Clinical Activity of Autologous CD64 CAR T Cells in Patients With Relapsed and/or Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (HR-MDS)
University of Colorado, Denver
Summary
This is a Phase 1, open label, dose-escalation study to evaluate the safety, expansion, persistence, and preliminary clinical activity of lentivirally transduced autologous T cells expressing anti-CD64 chimeric antigen receptors (CAR) expressing tandem CD3ζ and 4-1BB (CD3ζ/4-1BB) costimulatory domains in subjects with refractory or relapsed (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). This CAR T cell product will be referred to as "CD64 CAR T" which is CD64 directed, autologous, genetically modified CAR T cells. The primary objective identify the safety profile and maximum tolerated dose (MTD) of CD64 CAR T in subjects with R/R AML or MDS as determined by the defined DLTs using a standard Bayesian Optimal Interval (BOIN) design.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. ≥ 18 years of age. 2. Subjects must have one of the following diagnoses per the International Consensus Classification (ICC) 2022 criteria: 1. Acute Myeloid Leukemia (AML). 2. Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML). 3. MDS with excess blasts (MDS-EB). 3. Refractory OR relapsed AML, MDS/AML, or MDS-EB, defined as: a. Refractory disease i. Lack of at least PR after a minimum of 1 cycle of a hypomethylating agent (HMA) and venetoclax (Ven) combination (Ven/HMA) OR; ii. Lack of CRMRD- after a minimum of 3 cycles of Ven/HMA (MRD defined as ≥…
Interventions
- DrugCD64 CAR T Cells
CD64 CAR T is a lentiviral transduced autologous T cells expressing anti-CD64 chimeric antigen receptors (CAR) possessing tandem CD3ζ and 4-1BB (CD3ζ/4-1BB) costimulatory domains.
Location
- University of Colorado HospitalAurora, Colorado