CD64 CAR T Cell Therapy in Adults With Relapsed and/or Refractory AML or HR-MDS

NCT07347418 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 25-0718.cc
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Refractory Acute Myeloid Leukemia (AML); High-risk Myelodysplastic Syndrome (MDS); Relapsed Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)/AML; Myelodysplastic Syndrome; AML (Acute Myeloid Leukemia)

Keywords

AML; MDS; CD64; CAR T; CAR T cell

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 0 through Day 42

Secondary Outcomes (7)

• Manufacturability - Product Release Failure

  Day 0 (Infusion)

• Manufacturability - Dose Failures

  Day 0 (Infusion)

• Efficacy - Overall Response Rate (ORR)

  Day 28, Month 3, and Month 6

• Efficacy - Overall Survival

  Up to 12 months post infusion

• Efficacy - Progression Free Survival (PFS)

  From treatment to end of study

Study Arms (1)

Relapsed and/or Refractory AML and HR-MDS

EXPERIMENTAL

Patients with relapsed and/or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) will receive lymphodepleting chemotherapy followed by infusion of CD64 CAR T-cells, starting at dose level 1.

Drug: CD64 CAR T Cells

Interventions

CD64 CAR T Cells DRUG

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.

Relapsed and/or Refractory AML and HR-MDS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age.
• Subjects must have one of the following diagnoses per the International Consensus Classification (ICC) 2022 criteria:
• Acute Myeloid Leukemia (AML).
• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML).
• MDS with excess blasts (MDS-EB).
• 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 ≥ 0.1% blasts by multi-parameter flow cytometry).
• b. Relapsed disease i. Recurrence of \> 5% blasts in the bone marrow by morphology OR; ii. ≥ 0.1% blasts by multi-parameter flow cytometry when a previous bone marrow aspirate demonstrated MRD-negativity OR; iii. ≥ 0.1% blasts by multi-parameter flow cytometry ≥ 6 months post-allogeneic stem cell transplant AND no active graft-versus-host disease (GVHD) requiring immunosuppressive therapy.
• 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 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 109/L prior to apheresis. Hydroxyurea is permitted to achieve this.
• Absolute lymphocyte count (ALC) ≥ 200/µL prior to apheresis OR ALC \< 200 µL with concurrent lymphocyte subset analysis (CD3, CD4, and CD8 counts) confirming an absolute CD3 count ≥ 150/µL.
• Confirmed availability of cells for a rescue stem cell transplant AND subject must be deemed an appropriate candidate for such therapy per institutional standards.
• Subjects who have undergone prior allogeneic stem cell transplant must be ≥ 6 months out from transplant and be off systemic immunosuppression for at least 1 month at the time of enrollment.
• Adequate organ function, defined as:

You may not qualify if:

• Subjects with Acute Promyelocytic Leukemia (APL) with t(15;17)
• Receipt of previous chemotherapy for AML or MDS, as follows:
• a. Prior to apheresis, the following washout periods apply: i. Hydroxyurea: 1 day ii. Hypomethylating agent and/or venetoclax: 7 days iii. Small molecule targeted therapy (including tyrosine kinase inhibitors): 3 half-lives or 7 days, whichever is shorter.
• iv. Immune checkpoint inhibitors or other immunological agents: 5 half-lives or 28 days, whichever is shorter.
• v. Investigational products: 5 half-lives or 28 days, whichever is shorter. vi. Any other systemic chemotherapy: 14 days vii. Allogeneic stem cell transplantation: 180 days viii. Donor lymphocyte infusion (DLI): 60 days ix. Craniospinal or total body radiation: 42 days b. After apheresis and prior to lymphodepletion, no treatment for AML and MDS is permitted, with the exception of bridging hydroxyurea with a washout period of 1 day prior to the start of the lymphodepletion regimen.
• 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.
• Pregnant or lactating (nursing) women.
• Known HIV infection or active Hepatitis B or Hepatitis C infection.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
• Subjects with cardiac arrhythmia, or arrhythmias that are not stable with medical management, within 2 weeks of the Screening/Enrollment visit.
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• Evidence of another uncontrolled malignancy.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Mathew Angelos, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derek Schatz

CONTACT

720-848-0628; derek.schatz@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants receive CD64 CAR T cells. There is no control arm.

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: January 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

US (1)