Graft Versus Host DiseasePhase 1NCT02526329
Donor Regulatory T Cells in Treating Patients With Visceral Acute Graft-versus-Host Disease After Stem Cell Transplant
A Phase 1 study testing donor regulatory T lymphocytes and laboratory biomarker analysis in people with Graft Versus Host Disease, run by Everett Meyer at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- donor regulatory T lymphocytes and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2015to Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- DONOR: HIV positive
- DONOR: Pregnant donor
- DONOR: Factors which place the donor at increased risk for complications from leukapheresis
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Hospitals and Clinics
Stanford, California, 94305
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- Being tested
- donor regulatory T lymphocytes, laboratory biomarker analysis
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donor regulatory T lymphocytesBiological
Also called donor CD4+CD25+FoxP3+ T cells
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: donor regulatory T lymphocytes; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (6)
Incidence of grade 3 or higher non-GVHD infusion-related adverse events
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
Measured: Up to day 28
Grade 4 (life threatening) or 5 (fatal) adverse events
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
Measured: 28 days
Grade 4 (life threatening) respiratory distress
Grade 4 (life threatening) respiratory distress within 72 hours of Treg infusion will be reported
Measured: 72 hours
Change in blood Treg cell numbers following the infusions
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 the hypotheses of no change from baseline to post infusion.
Measured: Baseline to up to day 28
Overall survival (OS)
The OS will be estimated by the Kaplan-Meier product-limit method, with standard confidence limits.
Measured: Day 100
Incidence of cGVHD.
Incidence of cGVHD will be reported at Post HCT day +180
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study start6 Aug 2015
- Primary completionNov 2022 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Logistics
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Everett Meyer
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Everett Meyer, Stanford University
- Investigators
- Everett Meyer, Principal investigator, Stanford University Hospitals and Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02526329
- Sponsor's protocol ID
- IRB-30861
- Other IDs
- NCI-2014-01609, IRB-30861, BMT267
- Status last verified
- Nov 2023
- First submitted
- 14 Aug 2015
- Last updated
- 22 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02526329
- Acronym / sponsor ID
- IRB-30861
- Conditions
- Graft Versus Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistics
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Everett MeyerUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 6 Aug 2015 (actual)
- Primary completion
- Nov 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 18 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (donor regulatory T lymphocytes) | Experimental | Biological: donor regulatory T lymphocytes, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| donor regulatory T lymphocytesAlso: donor CD4+CD25+FoxP3+ T cellsGiven IV | Biological | Treatment (donor regulatory T lymphocytes) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (donor regulatory T lymphocytes) |
Primary outcome
Incidence of grade 3 infusion reaction within 24 hours of infusion
Time frame: 24 hours
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.
6 secondary outcomes
Incidence of grade 3 or higher non-GVHD infusion-related adverse events
Time frame: Up to day 28
Grade 4 (life threatening) or 5 (fatal) adverse events
Time frame: 28 days
Grade 4 (life threatening) respiratory distress
Time frame: 72 hours
Change in blood Treg cell numbers following the infusions
Time frame: Baseline to up to day 28
Overall survival (OS)
Time frame: Day 100
Incidence of cGVHD.
Time frame: 180 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Everett Meyer principal investigator
Stanford University Hospitals and Clinics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing donor regulatory T lymphocytes and laboratory biomarker analysis in people with Graft Versus Host Disease, run by Everett Meyer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of grade 3 infusion reaction within 24 hours of infusion (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.