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). 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 of the study is to identify the safety profile and maximum tolerated dose (MTD) of CD64 CAR T in subjects with R/R AML as determined by the defined DLTs using a standard Bayesian Optimal Interval (BOIN) design.
≥ 18 years of age.
Subjects must have received at least one prior line of therapy, including at least one line of therapy containing Ven.
Documentation of CD64 expression on ≥70% of myeloid blasts by flow cytometry after the most recent relapse, as determined by standardized and validated multiparameter flow cytometry assay (Hematologics, Inc., Seattle, WA).
Total white blood cell (WBC) count ≤ 25 x 10(to the 9th)/L prior to apheresis. Hydroxyurea is permitted to achieve this
Subjects with Acute Promyelocytic Leukemia (APL) with t(15;17)
Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
Previous treatment with investigational gene or cell therapy (including CAR therapy).
Signs or symptoms indicative of CNS leukemia involvement. A CNS evaluation should be performed if CNS involvement is suspected to rule out CNS leukemia involvement.
Single group
CD64 CAR T Cells
DrugCD64 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.
Maximum Tolerated Dose (MTD)
MTD will be established from the DLTs, which will be considered from the time of CD64 CAR T infusion (Day 0) through Day 42 after the subject's last infusion. A DLT is a treatment-emergent adverse event, or a clinically significant abnormal laboratory value, observed during the DLT observation period.
Manufacturability - Product Release Failure
The proportion of CD64 CAR T products that fail to meet the product release criteria, out of the number of enrolled subjects in whom manufacturing was attempted.
Manufacturability - Dose Failures
The proportion of CD64 CAR T products that fail to meet the assigned dose, out of the number of subjects enrolled for whom manufacturing was attempted.
Efficacy - Overall Response Rate (ORR)
The efficacy of the CD64 CAR T-cell product will be assessed by determining the overall response rate (ORR) through morphologic evaluation of bone marrow at Day 28 post-infusion. Response categories include complete remission (CR), CR with measurable residual disease negative (CR MRD-), CR with incomplete hematologic recovery (CRi), CR with partial hematologic recovery (CRh), morphological leukemia-free state (MLFS), and partial response (PR).
Efficacy - Overall Survival
Overall Survival (OS) will be measured from date of CD64 CAR T-cell infusion until death from any cause. At one year post-infusion, OS will be analyzed using Kaplan-Meier estimates.
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