Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.

NCT06071624 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0840
• 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-directed chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory CMML. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells.

Conditions

Chronic Myelomonocytic Leukemia

Keywords

Chronic Myelomonocytic Leukemia; T Cell; Cell Therapy; CAR-T; chimeric antigen

Outcome Measures

Primary Outcomes (2)

• Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the dose limiting toxicity (DLT) of the CD4CAR in CMML

  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

• The efficacy of treatment with CD4CAR and description of CMML response to CD4CAR

  serial marrow sampling will be analysed for response as measured by reduction on the CMML clonal cells at different time points. Other measures include reduction on transfusion dependency and molecular remissions if at diagnoosis molecular markers were identified.

  Day 28 through 6 months post-infusion

Secondary Outcomes (2)

• in vivo persistence of a single dose of the CD4CAR in subjects with CMML

  Day 0 through Day 28

• efficiacy of the CD4CAR to target T regulatory cells and myeloid derived suppressor cells

  Day 0 through Day 28 post-infusion

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

You may qualify if:

• ≥ 18 years old at the time of informed consent
• Ability to provide written informed consent and HIPAA authorization
• Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment.
• Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator)
• ALT/AST \< 3 x ULN
• Bilirubin \< 2 x ULN
• No supplemental oxygen at rest Note: Pulmonary Function Test (PFT) only required per treating physician discretion.
• Adequate cardiac function with EF of ≥50%. This will not have to be repeated if within 45 days of initial assessment
• Adequate venous access for apheresis and no other contraindications for leukapheresis

You may not qualify if:

• CD4 negative CMML
• 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 or hepatitis C 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 uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator
• HIV infection

Sponsors & Collaborators

• Huda Salman: lead
• iCell Gene Therapeutics: collaborator
• The Leukemia and Lymphoma Society: collaborator

Study Sites (4)

University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136

Miami, Florida, 33136, United States

RECRUITING

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Albert Einstein Health Network

The Bronx, New York, 10467, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Huda Salman, MD, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Roach, RN

CONTACT

317-274-0840; jeschwar@iu.edu

Jennifer Schwartz, MD, PhD

CONTACT

317-274-0840; jeschwar@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: September 15, 2023
• First Posted: October 6, 2023
• Study Start: February 21, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2043
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

US (4)