Donor Regulatory T Cells in Treating Patients With Visceral Acute Graft-versus-Host Disease After Stem Cell Transplant

NCT ID: NCT02526329

Last Updated: 2023-11-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-06
• Study Completion Date: 2023-06-30

Brief Summary

This phase I trial studies the side effects and best dose of donor regulatory T cells in treating patients with graft-versus-host disease affecting the liver or gastrointestinal organs (visceral) within 100 days (acute) after undergoing a stem cell transplant. Graft-versus-host disease occurs when donor immune cells infused in a stem cell transplant attack the gut, skin, liver, or other organ systems of the patient. Regulatory T cells are a type of immune cell that may be able to reduce the attack of the donor's immune cells on the patient's normal cells and help treat graft-vs-host disease.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of donor T regulatory (Treg) cell infusions in subjects with visceral acute graft-versus-host disease (aGVHD) and incidence of dose limiting toxicities (DLTs) graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4 [v.4]) with a focus on infusion reactions within 24 hours, respiratory distress within 72 hours of infusion and all-cause mortality within 28 days of infusion.

SECONDARY OBJECTIVES:

I. Determine the quantitative blood Treg cell changes following the cell infusions.

II. Assess dosing requirements and treatment response rates to primary steroid, secondary and tertiary immunosuppressive therapy.

III. Post-transplant day +100 and day +180 survival. IV. Post-transplant incidence of chronic graft-versus-host disease (GVHD) at day +180.

OUTLINE: This is a dose-escalation study.

Patients receive donor regulatory T lymphocytes intravenously (IV) over 5 minutes or less on day 0. Some patients receive a second infusion of frozen donor regulatory T lymphocytes 5-7 days after the initial infusion or 2 additional infusions separated by 5-7 days.

After completion of study treatment, patients are followed up weekly until day 28 and then on days 100 and 180.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (donor regulatory T lymphocytes)

Patients receive donor regulatory T lymphocytes intravenously (IV) over 5 minutes or less on day 0. Some patients receive a second infusion of frozen donor regulatory T lymphocytes 5-7 days after the initial infusion or 2 additional infusions separated by 5-7 days.

Group Type: EXPERIMENTAL

donor regulatory T lymphocytes

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

donor regulatory T lymphocytes

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

donor CD4+CD25+FoxP3+ T cells

Eligibility Criteria

Inclusion Criteria

• Visceral aGVHD defined as: at least stage III/IV acute liver or stage II/III gastrointestinal (GI) GVHD by clinical criteria and/or GI and/or liver biopsy confirmation showing no alternative explanation for symptoms of GVHD
• Ability to understand and willingness to sign a written informed consent form
• Must have a 7/8 or 8/8 or haploidentical related donor matched at the human leukocyte antigen (HLA)-A, B, C, DRB1 who was evaluated and provided the donor transplant graft
• Myeloablative or non-myeloablative allogeneic hematopoietic cell transplantation
• Karnofsky performance status >= 50
• DONOR: Age >= 18 to =< 77 years old
• DONOR: Karnofsky performance status of >= 70% defined by institutional standards
• DONOR: Must be the same sibling donor from whom the recipient's blood and marrow graft was collected for the original allogeneic transplant that is HLA 7/8 or 8/8 or haploidentical matched at the HLA-A, B, C, and DRB1
• DONOR: Serologies for human immunodeficiency virus (HIV) antigen (Ag), HIV 1 and HIV 2 antibody (Ab), human T-cell lymphotropic virus (HTLV) 1 and HTLV 2 Ab, hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR)+, or hepatitis C Ab or PCR+, syphilis (Treponema) screen and HIV 1 and hepatitis C by NAT (nucleic acid testing) have been collected prior to apheresis
• DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within two weeks of apheresis
• DONOR: Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
• DONOR: Donor selection will be in compliance with 21 Code of Federal Regulations (CFR) 1271

Exclusion Criteria

• Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care
• Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
• Cytomegalovirus colitis or enteritis as defined by cytomegalovirus (CMV) shell vial or culture positivity from endoscopic biopsy the discretion of the treating physician based upon PCR positivity, clinical presentation and histology
• Respiratory insufficiency with oxygen requirement > 4 L nasal cannula
• Multi-organ failure
• DONOR: Evidence of active infection or viral hepatitis
• DONOR: HIV positive
• DONOR: Pregnant donor
• DONOR: Factors which place the donor at increased risk for complications from leukapheresis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Everett Meyer

OTHER

Sponsor Role: lead

Responsible Party

Everett Meyer

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Everett Meyer

Role: PRINCIPAL_INVESTIGATOR

Stanford University Hospitals and Clinics

Locations

Stanford University Hospitals and Clinics

Stanford, California, United States

Countries

United States

Other Identifiers

NCI-2014-01609

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB-30861

Identifier Type: OTHER

Identifier Source: secondary_id

BMT267

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-30861

Identifier Type: -

Identifier Source: org_study_id