Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant

NCT06197672 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0851
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory AML. The study will evaluate safety in this patient population and also the presence of efficacy signal described by elimination of residual disease to qualify patients for stem cell transplant.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; T Cell; Cell Therapy; CAR T; Chimeric Antigen Receptor Therapy

Outcome Measures

Primary Outcomes (4)

• 1. Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the Dose Limiting Toxicity (DLT) of the CD4CAR in AML. Optimal dose is highest safe dose that produces the most response.

  In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented.

  Day 0 through Day 28 post-infusion

• Persistence and biologic behavior of CD4CAR as measured by a. Serial blood and marrow sampling to detect CD4CAR over time post infusion. b. Serial testing for CD4CAR proliferation, differentiation and polarization if feasible overtime after infusion.

  The persistence of the CAR through day 28 and possibly longer if detected by D28. This will be performed by flow to assess for the CD3+/Fab2+ cell population The phenotype of the CAR will be determined by flow as well, to look for Tcm phenotype

  Day 0 Through Day28 post infusion

• 3. Determine the influence of CD4CAR on T regs

  1. Examine the efficacy of CD4CAR on changing the frequency of T regs subpopulation after CD4CAR infusion as compared to their frequency prior to treatment. 2. Determine the impact of the change in T regs and MDSCs abundance on objective response to CD4CAR.

  Day 0 through Day 28

• Determine the influence of CD4CAR on myeloiod derived suppressor cells, MDSCs

  Examine the efficacy of CD4CAR on changing the frequency of MDSCs subpopulation

  Day 0 through Day 28

Secondary Outcomes (3)

• Determine mLSCs frequency before and after the CD4CAR infusion

  Baseline through Day 30

• Quantification of CD4CAR associated cytokines

  Baseline through Day 30

• Describe disease response using European LeukemiaNet (ELN) 2022 recommendation

  Baseline through Day 30

Study Arms (1)

Treatment

EXPERIMENTAL

Redirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells)

Biological: CD4CAR

Interventions

CD4CAR BIOLOGICAL

CD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose

Treatment

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 12 years old at the time of informed consent
• Ability to provide written informed consent and HIPAA authorization.
• Diagnosis of AML that is CD4+ and must have failed standard induction/ first line treatment such as intensive induction or less intensive hypomethylation and venetoclax first line. In the specific case of azacitidine and venetoclax (aza/ven), BM biopsy for response assessment on days 21-28 of first cycle. If disease progression by increasing number of blasts is documented, patient will be eligible. If no morphologic remission (persistent BM blasts above 5%) but evidence of efficacy exists, a second cycle without interruption will be given with the goal of achieving morphologic remission and repeat BM biopsy on days 21-28 of this cycle. If residual disease or disease progression is captured, then they will be considered refractory and will qualify for this trial. This is unless the patient now qualifies for a more intensive induction therapy that they did not qualify for when aza/ven was initially chosen as first-line treatment. Given the low response rate for aza/ven in the RR-AML, CR of only 13%, this combination would not be a prerequisite to qualify for the study.
• If these patients who fail first line treatment have an FDA approved treatment options available (including targeted and non-targeted treatment) for a second line treatment, they do not qualify for the trial until they also are deemed nonresponsive to those. If an approved second line is not available, patients will be eligible after first line failure.
• Creatinine clearance of \> 60ml/min (or otherwise non clinically significant, per study investigator)
• alanine aminotransferase/ aspartate aminotransferase ALT/AST \< 3 x ULN
• Bilirubin \< 2 x ULN (UPPER LIMIT OF NORMAL)
• Pulmonary Function Test (PFT) with a DIFFUSE LUNG CAPACITY , DLCO, of ≥ 60% (if not completed within 6 months from Day 0)
• Adequate echocardiogram with EJECTION FRACTION, EF, of ≥50%
• Adequate venous access for apheresis and no other contraindications for leukapheresis
• Confirmation of a bone marrow donor for post CD4CAR transplant to proceed to transplant if eligible post treatment.

You may not qualify if:

• CD4 negative AML
• Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy.
• Uncontrolled active infection necessitating systemic therapy.
• Active hepatitis B hb, or hepatitis C, HC, infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit.
• Note the following subjects will be eligible:
• Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible.
• Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible.
• Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible.
• If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
• Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
• Subjects who receive daily corticosteroids in replacement doses can be included in the study. The replacement doses are defined as following:
• Hydrocortisone 25mg/day or less
• Prednisone 10mg/day or less
• Any previous treatment with any gene therapy products
• Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator

Sponsors & Collaborators

• Huda Salman: lead
• iCell Gene Therapeutics: collaborator

Study Sites (4)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Huda Salman, MD, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Roach, RN

CONTACT

(317) 274-0840; cmroach@iu.edu

Huda Salman, MD, PhD

CONTACT

317-278-9504; hsalman@iu.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 INVESTIGATOR
• PI Title: Director, Hematologic Malignancies Service and Director, CAR T Cellular Therapy Program

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: January 9, 2024
• Study Start: March 19, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2042
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (4)