Phase I Study of CD4-Directed CAR T-Cell Therapy for Relapsed or Refractory CD4 T-Cell Leukemia and Lymphoma

What this Trial Is About

Researchers are conducting a Phase I, open-label, multicenter trial to study CD4-directed chimeric antigen receptor T-cells CD4CAR in patients with relapsed or refractory CD4-positive T-cell leukemia and lymphoma. The study aims to evaluate the safety and feasibility of administering these engineered T-cells, which target CD4 on malignant cells. The trial is designed to include about 20 patients, with an expected treatment of 15 after accounting for dropouts due to disease progression or manufacturing failures. Participants will undergo a dose-escalation protocol where their own T-cells are collected through apheresis, engineered to express the CD4CAR construct, expanded, and then infused back intravenously as a single dose. Before infusion, patients receive conditioning chemotherapy to reduce tumor burden. The manufacturing process takes approximately 3 to 4 weeks, and dosing follows a traditional 33 design with escalating cell doses to determine the recommended dose for future studies. Post-infusion, patients will be closely monitored for treatment-related toxicities and immune responses. During the study, participants will have frequent blood tests to monitor cytokine levels, CD4CAR cell presence, and immune reactions at multiple timepoints up to 42 days after infusion. Tumor burden will be assessed weekly for six months, followed by quarterly clinical evaluations for two years. Long-term follow-up will continue up to 15 years via phone and questionnaires to track survival, relapse, and new malignancies. Safety monitoring includes infection surveillance and standard prophylaxis for immune-compromised patients.

CD4CAR for CD4+ Leukemia and Lymphoma