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

NCT05993611 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 22375NCI-2023-04067P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity

  Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0; cytokine release syndrome and immune effector cell associated neurotoxicity syndrome will be assessed per American Society for Transplantation and Cellular Therapy consensus criteria. Observed toxicities will be summarized by type, severity, date of onset, duration, reversibility, and attribution.

  From infusion of Allogeneic CD6 chimeric antigen receptor T regulatory cells (CD6-CAR Tregs) to day +28

• Feasibility as the ability to met at least 80% of the required cell dose at the assigned dose level

  Will be estimated with 90% confidence interval (CI) overall and by dose level.

  From infusion of CD6-CAR Tregs to day +28

• Feasibility as the ability to meet the required produce release criteria

  Will be estimated with 90% CI overall and by dose level.

  From infusion of CD6-CAR Tregs to day +28

Secondary Outcomes (7)

• CD6-CAR Treg activity

  Up to 15 years

• Changes in cGVHD severity

  Baseline up to 15 years

• Failure-free survival (FFS)

  From infusion of CD6-CAR Tregs to start of new treatment for cGVHD, recurrence of malignancy, or death, whichever comes first, assessed at week 12 and 1-year follow-up

• Relapse-free survival

  From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years

• CD6-CAR Treg persistence

  Up to 15 years

Study Arms (1)

Treatment (CD6-CAR Treg, tafasitamab)

EXPERIMENTAL

Donors undergo leukapheresis over 2-4 hours for collection of 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 ECHO, 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 MRI/CT as clinically indicated on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Biological: Chimeric Antigen Receptor T-Cell Therapy; Procedure: Computed Tomography; Procedure: Echocardiography; Other: Electronic Health Record Review; Procedure: Leukapheresis; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Biological: Tafasitamab; Procedure: X-Ray Imaging

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (CD6-CAR Treg, tafasitamab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (CD6-CAR Treg, tafasitamab)

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Given CD6-CAR Tregs IV

Also known as: CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell Infusion

Treatment (CD6-CAR Treg, tafasitamab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (CD6-CAR Treg, tafasitamab)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (CD6-CAR Treg, tafasitamab)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (CD6-CAR Treg, tafasitamab)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (CD6-CAR Treg, tafasitamab)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (CD6-CAR Treg, tafasitamab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI/CT

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (CD6-CAR Treg, tafasitamab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (CD6-CAR Treg, tafasitamab)

Tafasitamab BIOLOGICAL

Given IV

Also known as: Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer, Monjuvi, MOR-00208, MOR00208, MOR208, Tafasitamab-cxix, XmAb5574

Treatment (CD6-CAR Treg, tafasitamab)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (CD6-CAR Treg, tafasitamab)

Eligibility Criteria

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

You may qualify if:

• All participants must have the ability to understand and the willingness to sign a written informed consent
• Participants must agree to allow the use of archival tissue from diagnostic biopsies.
• If unavailable, exceptions may be granted with study PI approval Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed
• Age \>= 18 years
• Karnofsky performance status of \>= 70%
• Received allogeneic hematopoietic stem cell transplantation (alloHCT) from matched related or haploidentical donor as part of treatment of hematologic disorders Note: The donor needs to consent for leukapheresis
• Clinical diagnosis of steroid-dependent or refractory, moderate to severe cGVHD
• Steroid refractory cGVHD defined as having persistent signs and symptoms of cGVHD per institutional policy despite the use of prednisone for 2 months without complete resolution of signs and symptoms
• Estimated life expectancy \> 90 days
• Stable dose of corticosteroids for \>= 14 days prior to enrollment not exceeding 15mg/day of prednisone or equivalent + with up to 7ng/mL/day sirolimus with therapeutic drug monitoring
• Exposure to at least 1 of the Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI) therapies for cGVHD
• Naive to anti-CD6 therapy post most recent alloHCT
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (without myeloid growth factors within 1 week of study entry) (performed within 28 days prior to enrollment)
• Platelets \>= 50,000/mm\^3 (performed within 28 days prior to enrollment) NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
• Total bilirubin =\< 2 mg/dL (exception permitted in patients with Gilbert's syndrome), unless hepatic dysfunction is a manifestation of presumed cGVHD) (performed within 28 days prior to enrollment) NOTE: Abnormal liver function tests (LFTs) (liver function panel) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation

You may not qualify if:

• Immunosuppressive therapy within 28 days prior to enrollment (exception: corticosteroid)
• Concurrent other investigational agents, including biologics
• Vaccines within 28 days prior to enrollment
• Donor lymphocyte infusion within 100 days of enrollment
• No known contraindications to steroids or tocilizumab
• No current active malignancy\* (Exception: Basal or squamous cell carcinoma)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Active uncontrolled infection requiring systemic antibiotics and/or anti-virals
• Other autoimmune/inflammatory disorders
• Clinically significant uncontrolled illness
• History of vascular disease (e.g., deep vein thrombosis, stroke)
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Uncontrolled atrial fibrillation or hypertension

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Hematologic Diseases

Interventions

Biopsy; Specimen Handling; Immunotherapy, Adoptive; Leukapheresis; Spinal Puncture; Magnetic Resonance Spectroscopy; tafasitamab; Immunoglobulins; Disulfides; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Diagnostic Techniques, Neurological; Punctures; Spectrum Analysis; Chemistry Techniques, Analytical; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Amandeep Salhotra

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: August 15, 2023
• Study Start: February 19, 2024
• Primary Completion (Estimated): May 21, 2028
• Study Completion (Estimated): May 21, 2028
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (1)