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

NCT02526329 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-30861NCI-2014-01609BMT267
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3 infusion reaction within 24 hours of infusion

  Dose-limiting toxicity will be defined as CTCAE Grade 3 or higher cytokine/release syndrome/acute infusion reaction within 24 hours after Treg cell infusion. The rates of defined DLTs will be calculated and the one-sided upper 80%, 90%, and 95% confidence limits calculated.

  24 hours

Secondary Outcomes (6)

• Incidence of grade 3 or higher non-GVHD infusion-related adverse events

  Up to day 28

• Grade 4 (life threatening) or 5 (fatal) adverse events

  28 days

• Grade 4 (life threatening) respiratory distress

  72 hours

• Change in blood Treg cell numbers following the infusions

  Baseline to up to day 28

• Overall survival (OS)

  Day 100

Study Arms (1)

Treatment (donor regulatory T lymphocytes)

EXPERIMENTAL

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.

Biological: donor regulatory T lymphocytes; Other: laboratory biomarker analysis

Interventions

donor regulatory T lymphocytes BIOLOGICAL

Given IV

Also known as: donor CD4+CD25+FoxP3+ T cells

Treatment (donor regulatory T lymphocytes)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (donor regulatory T lymphocytes)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Everett Meyer: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Everett Meyer

  Stanford University Hospitals and Clinics

  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 INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 18, 2015
• Study Start: August 6, 2015
• Primary Completion: November 1, 2022
• Study Completion: June 1, 2023
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)