NCT05993611

Allogeneic CD6 Chimeric Antigen Receptor T Regulatory Cells (CD6-CAR Tregs) for the Treatment of Patients With Chronic Graft Versus Host Disease After Allogeneic Hematopoietic Cell Transplantation

A First-in-Human Study to Evaluate the Safety, Feasibility and Tolerability of Allogeneic CD6 Chimeric Antigen Receptor T Regulatory Cells (CD6-CAR Tregs) in Patients With Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Cell Transplantation (alloHCT)

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of allogeneic CD6 chimeric antigen receptor T regulatory cells (CD6-CAR Tregs) in treating patients who have chronic graft versus host disease (cGVHD) after an allogeneic hematopoietic cell transplantation (HCT). An allogeneic HCT is an established treatment for benign or malignant blood and marrow conditions where healthy stem cells from a donor are infused into a patient to help the patient's bone marrow make more healthy cells and platelets. GVHD is a systemic disorder that occurs when the graft's immune cells recognize the host as foreign and attack the recipient's body cells. "Graft" refers to transplanted, or donated tissues, and "host" refers to the tissues of the recipient. It is a common complication after allogeneic HCT. The onset of cGVHD is usually within three years of transplantation and has some features of autoimmune diseases. A strategy that minimizes the incidence and severity of cGVHD, without other adverse effects, is needed to improve survival after allogeneic HCT. T regulatory cells are critical for controlling autoimmunity and maintaining immune homeostasis. Patients with active cGVHD have reduced numbers of T regulatory cells compared to patients without GVHD, suggesting that restoration of T regulatory cells in patients with active cGCHD is impaired and insufficient numbers may contribute to cGVHD. Therefore, therapies that augment numbers and function of T regulatory cells may promote tolerance and control of cGVHD. CAR T-cell therapy is a type of treatment in which T cells (a type of immune system cell) are taken from the blood and changed in the laboratory. The gene for a special receptor that binds to a certain protein, CD6, on the patient's cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CD6-CAR Tregs combines the CD6-targeted anti-inflammatory response with the immune regulatory properties of T regulatory cells which could generate a more potent and stable T regulatory cell population to promote immune tolerance and long-term disease control in cGVHD.

Detailed description

PRIMARY OBJECTIVES: I. Determine if CD6-CAR Tregs administration is safe and tolerable in patients who developed chronic graft-versus-host disease (cGVHD), by evaluation of toxicities, including: type, frequency, severity, attribution, time course and duration. II. To evaluate the feasibility to produce donor derived CD6-CAR Tregs. SECONDARY OBJECTIVES: I. Obtain preliminary evidence of CD6-CAR Tregs activity against cGVHD by estimating the response rate (as defined by 2014 National Institute of Health \[NIH\] consensus development project on clinical trials in cGVHD). II. Evaluate changes in cGVHD severity using physician -reported cGVHD activity assessment form. III. Evaluate changes in symptom activity using cGVHD activity assessment patient self-report. IV. Evaluate failure-free survival (FFS). V. Quantify CD6-CAR Treg cells in peripheral blood. VI. Characterize and assess changes in immune biomarkers over time in blood samples. EXPLORATORY OBJECTIVES: I. Percent and counts from peripheral blood T cell subsets in hematopoietic stem/progenitor cell compartments to assess ability of CD6-CAR Tregs to suppress pathogenic T cell activity and proliferation. II. Profile cytokine levels over time and changes to assess the ability of CD6-CAR Tregs to down-regulate proinflammatory cytokine production (IFNgamma, IL-6, TNFalpha) and adhesion molecules that promote pathogenic T cell. III. For subjects who receive tafasitamab-cxix for CAR Treg ablation, describe the activity of infusional tafasitamab-cxix to eliminate transferred CD6 CAR Treg cells. OUTLINE: This is a dose-escalation study of CD6-CAR Treg cells followed by a dose-expansion study. Donors undergo leukapheresis over 2-4 hours for collection of peripheral blood mononuclear cells (PBMSc) and the manufacturing of CD6-CAR Treg cells over 2 weeks. Patients then receive CD6-CAR Treg intravenously on day 0. Patients may also receive ablation tafasitamab IV post Treg cell infusion on days 1, 4, 8, 15, 22 for 1 cycle. If ablation is not complete by day 28, patients may receive an additional 1-2 cycles per investigator's discretion. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), computed tomography (CT), and x-ray imaging during screening and as clinically indicated. Patients undergo blood specimen collection on study and during follow-up. Patients may undergo a biopsy on study as well as a lumbar puncture and magnetic resonance imaging (MRI)/CT as clinically indicated on study. After completion of study treatment, patients are followed up to 28 days, monthly for 1 year, and then yearly for 15 years.

Conditions

• Chronic Graft Versus Host Disease
• Hematologic and Lymphocytic Disorder
• Steroid Refractory Graft Versus Host Disease

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Chimeric Antigen Receptor T-Cell Therapy	Given CD6-CAR Tregs IV
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Echocardiography	Undergo ECHO
OTHER	Electronic Health Record Review	Ancillary studies
PROCEDURE	Leukapheresis	Undergo leukapheresis
PROCEDURE	Lumbar Puncture	Undergo lumbar puncture
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI/CT
OTHER	Quality-of-Life Assessment	Ancillary studies
BIOLOGICAL	Tafasitamab	Given IV
PROCEDURE	X-Ray Imaging	Undergo x-ray imaging

Timeline

• Start date: 2024-02-19
• Primary completion: 2028-05-21
• Completion: 2028-05-21
• First posted: 2023-08-15
• Last updated: 2025-11-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study