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

Everett Meyer

Status and phase

Withdrawn

Phase 1

Conditions

Graft Versus Host Disease

Treatments

Other: laboratory biomarker analysis

Biological: donor regulatory T lymphocytes

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02526329

IRB-30861 (Other Identifier)

BMT267 (Other Identifier)

NCI-2014-01609 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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