This trial is active, not recruiting.

Condition graft versus host disease
Treatments donor regulatory t lymphocytes, laboratory biomarker analysis
Phase phase 1
Sponsor Everett Meyer
Collaborator National Cancer Institute (NCI)
Start date August 2015
End date October 2017
Trial size 12 participants
Trial identifier NCT02526329, 30861, BMT267, NCI-2014-01609, P30CA124435


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
donor regulatory t lymphocytes donor CD4+CD25+FoxP3+ T cells
Given IV
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Incidence of grade 3 infusion reaction within 24 hours of infusion, grade 4 respiratory distress within 72 hours of infusion, and grade 5 treatment related mortality or grade 3 or higher non-GVHD infusion-related adverse events according to the CTCAE v4
time frame: Up to day 28

Secondary Outcomes

Change in blood Treg cell numbers following the infusions
time frame: Baseline to up to day 28
Yield of Treg isolation
time frame: Up to day 28
Success of meeting the target dose
time frame: Up to day 28
Change in primary immunosuppressive requirements
time frame: Baseline to up to day 28
Change in secondary immunosuppressive requirements
time frame: Baseline to up to day 28
Overall survival (OS)
time frame: Day 100
time frame: Day 180
Incidence of chronic GVHD
time frame: Day 180

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase 1 Single Center Safety and Feasibility Study of Primary T Regulatory Cell Therapy to Treat Visceral Acute Graft-versus-Host Disease Following Hematopoietic Cell Transplantation
Principal investigator Everett Meyer
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Stanford University.
Location data was received from the National Cancer Institute and was last updated in June 2016.