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

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.

Conditions

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

Interventions

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Amandeep Salhotra · City of Hope Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-02-19

Primary Completion

2028-05-21

Completion

2028-05-21

FDA Drug

Yes

Countries

• United States

Study Locations