Stanford, California 94305

  • Graft Versus Host Disease

Purpose:

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.


Study summary:

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.


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


Study is Available At:


Original ID:

IRB-30861


NCT ID:

NCT02526329


Secondary ID:

NCI-2014-01609


Study Acronym:


Brief Title:

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


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


Overall Status:

Suspended


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Stanford University


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:

Logistics


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

12


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Everett Meyer
Principal Investigator
Stanford University Hospitals and Clinics

Study Dates

Start Date:August 2015
Completion Date:December 2024
Completion Type:Anticipated
Primary Completion Date:December 2023
Primary Completion Type:Anticipated
Verification Date:April 2019
Last Changed Date:April 19, 2019
First Received Date:August 14, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Incidence of grade 3 infusion reaction within 24 hours of infusion
Time Frame:24 hours
Safety Issues:False
Description: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
Outcome Type:Secondary Outcome
Measure:Incidence of grade 3 or higher non-GVHD infusion-related adverse events
Time Frame:Up to day 28
Safety Issues:False
Description:Incidence of grade 3 or higher non-GVHD infusion-related adverse events according to the CTCAE v4 that are not anticipated following HCT will be reported
Outcome Type:Secondary Outcome
Measure:Grade 4 (life threatening) or 5 (fatal) adverse events
Time Frame:28 days
Safety Issues:False
Description:Grade 4 (life threatening) or 5 (fatal) adverse events within after 28 days of Treg infusion that were otherwise unexpected in the immediate post transplant setting will be reported
Outcome Type:Secondary Outcome
Measure:Grade 4 (life threatening) respiratory distress
Time Frame:72 hours
Safety Issues:False
Description:Grade 4 (life threatening) respiratory distress within 72 hours of Treg infusion will be reported
Outcome Type:Secondary Outcome
Measure:Change in blood Treg cell numbers following the infusions
Time Frame:Baseline to up to day 28
Safety Issues:False
Description:The change in Treg cell counts from baseline to post infusion will be depicted in boxplots of both relative proportion and absolute numbers. Mean log (fold change) and confidence intervals will be calculated. The confidence intervals will be used to test
Outcome Type:Secondary Outcome
Measure:Overall survival (OS)
Time Frame:Day 100
Safety Issues:False
Description:The OS will be estimated by the Kaplan-Meier product-limit method, with standard confidence limits.
Outcome Type:Secondary Outcome
Measure:Incidence of cGVHD.
Time Frame:180 days
Safety Issues:False
Description:Incidence of cGVHD will be reported at Post HCT day +180

Study Interventions

Intervention Type:Biological
Name:donor regulatory T lymphocytes
Description:Given IV
Arm Name:Treatment (donor regulatory T lymphocytes)
Other Name:donor CD4+CD25+FoxP3+ T cells
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Treatment (donor regulatory T lymphocytes)

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (donor regulatory T lymphocytes)
Description: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.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Everett Meyer
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: March 26, 2020

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