CD4CAR for CD4+ Leukemia and Lymphoma

NCT03829540 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CTO-IUSCCC-ICG122-101FD-R-006820-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

This study is designed as a single arm open label Phase I, 3x3, multicenter study of CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory T-cell leukemia and lymphoma. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells. Funding Source - FDA OOPD

Conditions

T-cell Lymphoma; T-cell Leukemia

Keywords

CD4; T-cell; lymphoma; leukemia; chimeric antigen; CAR-T

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  To assess the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) according to CTCAE grading. The feasibility of treating those adverse events and their duration till resolution will also be described.

  18-24 months

Secondary Outcomes (9)

• Duration of in vivo survival of the CD4CAR.

  18-24 months

• Rate of manufacturing failure

  18-24 months

• Clinical Response

  18-24 months

• Trafficking of CD4CAR at tumor sites and at sites with significant toxicity

  18-24 months

• Number of participants with immune reactions against CD4CAR

  18-24 months

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:

• In order to be eligible to participate in this study, an individual will be enrolled if they meet the following criteria:
• Patients must voluntarily sign and date informed consent forms that state his or her willingness to comply with all study procedures and availability for the duration of the study.
• Age 12 years old or older
• Subjects with any documented CD4+ T cell hematologic malignancies. Male and female subjects with CD4+ T-cell hematologic malignancies with either relapsed or refractory disease (including those patients who have undergone a prior transplant (if allogeneic, subjects are eligible if there are no remaining donor cells) and patients with an inadequate response after 4-6 cycles of standard chemotherapy) are eligible. Response criteria for each disease subset will be evaluated based on Standard of Care Guidelines.
• 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%
• Adequate venous access for apheresis and no other contraindications for leukapheresis

You may not qualify if:

• 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 nondetectable 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 (unless as a part of a standard of care salvage therapy or conditioning protocol), 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, pseudorheumatism, emotional disturbances, etc) precipitated by the temporary stoppage.
• 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 study chair
• HIV infection.
• Subjects declining to consent for treatment

Sponsors & Collaborators

• Huda Salman: lead
• iCell Gene Therapeutics: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (6)

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

Albert Einstein Health Network

New York, New York, 10467, United States

RECRUITING

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

ACTIVE NOT RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, T-Cell; Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Hematologic Diseases

Study Officials

• Huda Salman, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Roach, RN

CONTACT

317-274-0840; cmroach@iu.edu

Huda Salman, MD

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, Brown Center for Immunotherapy, Don Brown Professor of Immunotherapy

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: February 4, 2019
• Study Start: July 9, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2041
• Last Updated: April 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)