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Graft Versus Host DiseasePhase 1NCT01911039

Phase 1 Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic GVHD

A Phase 1 study testing Regulatory T Cells in people with Graft Versus Host Disease and Allogeneic Hematopoietic Cell Transplant Recipient, run by Laura Johnston at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Chronic graft versus host disease (cGVHD) is a common complication of bone marrow or hematopoietic cell transplant from another person (allogeneic transplant). This study will determine if subjects with steroid dependent/refractory cGVHD can tolerate infusion of donor regulatory T cells and whether their cGVHD… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Regulatory T Cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Jul 2013to 31 Jul 2018
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

  • Steroid dependent/refractory cGVHD defined as:
  • Steroid dependent disease: Persistent cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg orally [po] every other day) for at least 12 weeks
  • Steroid refractory disease: Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg po every other day) for at least 4 weeks
  • Participants must be receiving systemic glucocorticoid therapy for cGVHD; all immunosuppressive therapy may include but not be limited to tacrolimus, sirolimus, CellCept, cyclosporine, and systemic corticosteroid must be at stable doses for 28 days prior to the first cell infusion
  • Chronic GVHD manifestations that can be followed on physical or laboratory exam; these include but are not necessarily limited to:
  • Skin changes
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  • Oral mucosa changes
  • Bronchiolitis obliterans
  • Ocular changes
  • Karnofsky performance status >= 60
  • Serum creatinine =< 2 mg/dL
  • Absolute neutrophil count (ANC) > 1 x 10^9/L
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 20 x upper limit of normal (ULN) or
  • Total bilirubin =< 10 x ULN
  • Allogeneic hematopoietic cell transplant recipient
  • Transfusion independent
  • Oxygen saturation during exertion is maintained at >= 88% on room air
  • Does not have clinically significant, symptomatic uncontrolled heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
  • DONOR: Age >= 18 to =< 75 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 human leukocyte antigen (HLA) 7/8 or 8/8 matched at the HLA-A, B,C, DRB1
  • DONOR: Serologies for human immunodeficiency virus (HIV) antigen (Ag), HIV 1 and HIV 2 antibody (Ab), human T-lymphotropic virus type I (HTLV 1) and HTLV 2 Ab, hepatitis B surface antigen (sAg) or polymerase chain reaction positive (PCR+), or hepatitis C Ab or PCR+, Syphilis (Treponema) screen and HIV 1 and hepatitis C by nucleic acid testing (NAT) 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 three 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

  • Original transplant utilized an unrelated donor graft
  • Uncontrolled infections that are not responsive to antimicrobial therapy
  • Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
  • Second malignancy except for skin cancer within the last 5 years
  • Received any investigational agent =< 28 days before Treg infusions
  • Received filgrastim (GCSF) treatment within one month of enrollment
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  • Received a donor lymphocyte infusion (DLI) or hematopoietic cell transplantation (HCT) within 3 months of enrollment
  • DONOR: Evidence of active infection or viral hepatitis
  • DONOR: HIV positive
  • DONOR: Pregnant donor

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University, School of Medicine

    Palo Alto, California, 94305

Other trials in United States

About this study

Official title: A Phase 1 Safety and Tolerability Study of Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic Graft Versus Host Disease

Chronic graft versus host disease (cGVHD) is a common complication of bone marrow or hematopoietic cell transplant from another person (allogeneic transplant). This study will determine if subjects with steroid dependent/refractory cGVHD can tolerate infusion of donor regulatory T cells and whether their cGVHD responds to the infusion.

Read the detailed description

PRIMARY OBJECTIVES:

Determine the safety and tolerability of donor T regulatory (Treg) cell infusions in subjects with steroid dependent/refractory chronic graft versus host disease.

SECONDARY OBJECTIVES:

  1. Determine the quantitative blood Treg cell changes following the cell infusions
  2. Determine clinical efficacy of donor Treg cells as failure-free survival (FFS) defined by the absence of a new immunosuppressive therapy added, non-relapse mortality, and recurrent malignancy at Day 180 after the first Treg infusion
  3. In addition to FFS, the study will measure the change in:
  4. cGVHD symptom burden measured by the Lee cGVHD Symptom Scale by increase in >7 points
  5. NIH organ-specific cGVHD scale
  6. The reduction in daily corticosteroid requirement of prednisone to <=0.25 mg/kg-day at Day 180 after the first Treg infusion
Being tested
Regulatory T Cells
Keywords
GVHD, cGVHD
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.

  • Regulatory T CellsBiological

    Also called donor Treg cell

Study groups in NCT01911039
Study groupRoleWhat they receive
Regulatory T CellsExperimentalCohort 1 at 1x105 Treg cells/kg, Cohort 2 at 5x105 Treg cells/kg and Cohort 3 at 1.5x106 Treg cells/kg with an extension phase at the MTD (or maximum administered dose if the MTD is not reached).
Receives: Biological: Regulatory T Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The frequency of adverse events related to the donor Treg infusions (e.g., grade III-IV aGVHD by the modified Keystone criteria and grade 3 or higher infusional toxicities graded according to the CTCAE v. 4)

    For infusion-related toxicities, recipients will be monitored for 1 hour after the Treg infusion. Additional toxicities which may occur during the first 28 days after the Treg infusions will count towards the assessment of safety and tolerability (DLT assessment) (e.g., development of aGVHD). Acute GVHD will be assessed using the modified Keystone criteria on Days 14, 28, 42, 56, 84 and 180 after the Treg infusion (or if the subject is exhibiting signs of aGVHD in-between study visits). Dose limiting toxicities are defined in Section 8. Only toxicities which occur during the first 28 days after the cell infusion will count towards the assessment of DLTs. A dose of Treg will be considered safe if DLTs occur in only 1/6 or 0/3 members of the cohort during the dose-escalation phase.

    Measured: Up to day 180

Secondary outcomes (5)

  1. Change in absolute blood Treg levels

    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.

    Measured: Baseline to day 42

  2. Improvement in Failure Free Survival (FFS) over cGVHD

    FFS is defined as the absence of a third line therapy (treatment failure). Estimated by the Kaplan-Meier product-limit method, with standard confidence limits.

    Measured: At day 180

  3. Successful achievement of cGVHD partial response or Complete response by the NIH consensus criteria

    1. Complete Response (CR) - Complete resolution of all reversible manifestations of cGVHD. Irreversible manifestations will be defined as (NIH consensus criteria) are: ocular xerosis, esophageal stricture, and bronchiolitis obliterans.
    2. Partial Response (PR) - At least a 25% absolute or 50% relative change (whichever is greater) when comparing start and end measurements in one cGVHD manifestation without worsening in the other manifestations.

    The results will be summarized in tabular form, with confidence intervals for the trinomial proportions.

    Measured: Up to day 180

  4. The ability to reduce steroid requirements to <0.25 mg/kg-day

    Measured: At day 180

  5. Change in >7 points on the Lee cGVHD Symptom scale relates to improvement in quality of life

    A one-sample t-test will be used on the change in scale from baseline to months 1, 3, and 6.

    Measured: Baseline to day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2013 (estimated)
  2. Study startJul 2013
  3. Primary completion31 Dec 2017
  4. Study completion31 Jul 2018

Resources

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
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01911039
Sponsor's protocol ID
IRB-27285
Other IDs
BMT253
Status last verified
Sep 2021
First submitted
15 Jul 2013
Last updated
27 Sep 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Regulatory T Cells in people with Graft Versus Host Disease and Allogeneic Hematopoietic Cell Transplant Recipient, run by Laura Johnston 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 25 inclusion and 10 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: finished, as of the sponsor's last update on 27 Sep 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The frequency of adverse events related to the donor Treg infusions (e.g., grade III-IV aGVHD by the modified Keystone criteria and grade 3 or higher infusional toxicities graded according to the CTCAE v. 4) (time frame: Up to day 180). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01911039.

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 27 Sep 2021.

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