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Chronic GVHDPhase 2/3NCT01106833

Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801)

A Phase 2/3 study testing Sirolimus + calcineurin inhibitor + prednisone and Sirolimus + prednisone in people with Chronic GVHD, run by Medical College of Wisconsin at 31 sites 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

This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Read more about this study

Who is it for?
Any age
Conditions the study is for
Chronic GVHD
What is being tested?
Sirolimus + calcineurin inhibitor + prednisone and Sirolimus + prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
31 sitesUnited States
Study dates
Apr 2010to Jun 2018
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Suitable candidates are patients with classic chronic GVHD or overlap syndrome (classic chronic plus acute GVHD)that is: a)Previously untreated (newly diagnosed) as defined by having received < 14 days of prednisone (or equivalent) before enrollment/randomization to study therapy; b)Previously treated but inadequately responding after ≤ 16 weeks of initial therapy with prednisone and/or calcineurin inhibitor (CNI) ± additional non-sirolimus agent (started at the time of chronic GVHD diagnosis).
  • Patient or guardian willing and able to provide informed consent.
  • Stated willingness to use contraception in women of childbearing potential.
  • Stated willingness of patient to comply with study procedures and reporting requirements.

Who cannot join

  • Patients with late persistent acute GVHD or recurrent acute GVHD only.
  • Inability to begin prednisone therapy at a dose of greater than 0.5 mg/kg/day.
  • Receiving sirolimus for treatment of chronic GVHD (sirolimus for prophylaxis or treatment of acute GVHD is acceptable).
  • Already receiving sirolimus (for prophylaxis or treatment of acute GVHD) with prednisone at ≥ 0.25 mg/kg/day (or equivalent) ± additional agents.
  • Receiving therapy for chronic GVHD for more than 16 weeks.
  • Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies.
Show all 14Show fewer
  • Inadequate renal function defined as measured creatinine clearance less than 50 mL/min/1.73 m^2 based on the Cockcroft-Gault formula (adults) or Schwartz formula (age less than or equal to 12 years). Adults: estimated creatinine clearance rate (eCCr) (mL/min/) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; Creatinine clearance (mL/min/1.73m^2) = eCCr x 1.73/Body Surface Area (BSA) (m^2); Children: eCCr (mL/min/1.73 m^2) = k x height (cm) / serum creatinine (mg/dL) k = 0.33 (pre-term), 0.45 (full term to 1 year old), 0.55 (age 1-12 years).
  • Inability to tolerate oral medications.
  • Absolute neutrophil count less than 1500 per microliter.
  • Requirement for platelet transfusions.
  • Pregnancy (positive serum β-HCG) or breastfeeding.
  • Receiving any treatment for persistent, progressive or recurrent malignancy.
  • Progressive or recurrent malignancy defined other than by quantitative molecular assays.
  • Known hypersensitivity to sirolimus.

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United States31 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48105-2967

  • Emory University

    Atlanta, Georgia, 30322

  • Blood & Marrow Transplant Program at Northside Hospital

    Atlanta, Georgia, 30342

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina Hospital at Chapel Hill

    Chapel Hill, North Carolina, 27599-7305

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Chicago

    Chicago, Illinois, 60637-1470

  • Jewish Hospital BMT Program

    Cincinnati, Ohio, 45236

  • University Hospitals of Cleveland/ Case Western

    Cleveland, Ohio, 44106-5061

  • City of Hope National Medical Center

    Duarte, California, 91010-3000

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • University of Florida College of Medicine (Shands)

    Gainesville, Florida, 32610-0277

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Texas/MD Anderson CRC

    Houston, Texas, 77030

  • University of Kansas Hospital

    Kansas City, Kansas, 66160

  • University of California San Diego Medical Center

    La Jolla, California, 92093

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792-5156

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10174

  • University of Oklahoma Medical Center

    Oklahoma City, Oklahoma, 73104

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-7680

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health & Science University (A) and (P)

    Portland, Oregon, 97239-3098

  • Virginia Commonwealth University/MCV Hospitals

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, New York, 55905

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109-1024

  • Washington University, Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • Stanford Hospital and Clinics

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase II/III Randomized, Multicenter Trial Comparing Sirolimus Plus Prednisone and Sirolimus/Calcineurin Inhibitor Plus Prednisone for the Treatment of Chronic Graft-versus-Host Disease (BMT CTN Protocol #0801)

This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to an experimental arm of one of the two pre-specified experimental arms (sirolimus + prednisone or the comparator arm of sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.

Read the detailed description

Background: Chronic GVHD is a medical condition that can become very serious. Chronic GVHD is a common development after allogeneic transplant that occurs when the donor cells attack and damage tissues. The primary purpose of this study is to compare treatment regimens that contain sirolimus without a calcineurin inhibitor to a comparator regimen of sirolimus with a calcineurin inhibitor and evaluate how well chronic GVHD responds to treatment. The combinations of medications in this study are:

  • Sirolimus + calcineurin inhibitor + prednisone
  • Sirolimus + prednisone

The goal is to select a treatment regimen for further comparison in the Phase III trial.

Design Narrative: The intent is to enroll subjects at the start of initial therapy for chronic GVHD, or before their chronic GVHD is refractory to glucocorticoid therapy, or is chronically dependent upon glucocorticoid therapy and multiple secondary systemic immunosuppressive agents. Patients will be stratified by transplant center and will be randomized to one of two arms.

Conditions
Chronic GVHD
Being tested
Sirolimus + calcineurin inhibitor + prednisone, Sirolimus + prednisone
Keywords
Chronic Graft-versus-Host Disease (cGVHD)
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sirolimus + calcineurin inhibitor + prednisoneDrug

    Also called Rapamune, Prograf, Neorall, Gengraf

    The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL.

    Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

  • Sirolimus + prednisoneDrug

    Also called Rapamune

    The target serum level for sirolimus is 3-12 ng/mL.

    Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Study groups in NCT01106833
Study groupRoleWhat they receive
calcineurin inhibitorActive comparatorSirolimus + calcineurin inhibitor + prednisone
Receives: Drug: Sirolimus + calcineurin inhibitor + prednisone
Sirolimus and prednisoneExperimentalSirolimus + prednisone
Receives: Drug: Sirolimus + prednisone

What is being measured

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

  1. Proportion of Participants With Treatment Success

    Treatment success was evaluated at 6 months in Phase II and is defined as a complete or partial response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death. In Phase III, treatment success was evaluated at 24 months and is defined as a complete response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death.

    Measured: 6 months and 24 months post-randomization

Secondary outcomes (16)

  1. Percentage of Participants With Overall Survival

    Overall survival is defined as survival of death from any cause.

    Measured: 6 months and 24 months post-randomization

  2. Percentage of Participants With Progression-free Survival

    Progression-free Survival is defined as survival without malignancy relapse. Relapse and death are considered failures for this endpoint.

    Measured: 6 months and 24 months post-randomization

  3. Percentage of Participants With Failure-free Survival

    Failure-free Survival is defined as survival without malignancy progression or initiation of secondary therapy for chronic GVHD. Progression, initiation of secondary therapy for chronic GVHD, and death are considered failures for this endpoint.

    Measured: 6 months and 24 months post-randomization

  4. Percentage of Participants With Relapse

    Relapse is defined as recurrence of the primary malignancy. Death is considered a competing risk for this endpoint.

    Measured: 6 months and 24 months post-randomization

  5. Percentage of Participants With Secondary Immunosuppressive Therapy Initiated

    The percentage of participants initiating secondary immunosuppressive therapy for chronic GVHD is described. Death is considered a competing risk for this endpoint.

    Measured: 6 months and 24 months post-randomization

  6. Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years

    The percentage of participants discontinuing all systemic immunosuppressive therapy by two years post-randomization is described. Death is considered a competing risk for this endpoint.

    Measured: 2 years post-randomization

  7. Prednisone Dose

    Daily dose of prednisone is described by treatment arm at baseline, 6 months, and 1 year post-randomization.

    Measured: Baseline, 6 months, and 1 year post-randomization

  8. Change in Prednisone Dose From Baseline

    Change in the daily dose of prednisone from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.

    Measured: 6 months and 1 year post-randomization

  9. Serum Creatinine Level

    Creatinine level is described by treatment arm at baseline, 6 months, and 1 year post-randomization.

    Measured: Baseline, 6 months, and 1 year post-randomization

  10. Change in Serum Creatinine Level From Baseline

    Change in creatinine level from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.

    Measured: 6 months and 1 year post-randomization

  11. Patient-reported Chronic GVHD Severity

    Each patient's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.

    Measured: Baseline, 6 months, 1 year, and 2 years post-randomization

  12. Provider-reported Chronic GVHD Severity

    Each patient's care provider's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.

    Measured: Baseline, 6 months, 1 year, and 2 years post-randomization

  13. NIH Consensus Criteria Chronic GVHD Severity

    Chronic GVHD severity was determined at baseline and at 6 months, 1 year, and 2 years post-randomization per the 2005 NIH Consensus Criteria (Filipovich et al. 2005). Severity is categorized as none, mild, moderate, and severe.

    Measured: Baseline, 6 months, 1 year, and 2 years post-randomization

  14. SF-36 Physical Component Summary

    The Medical Outcome Study SF-36 Physical Component Summary (PCS) is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

    Measured: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

  15. SF-36 Mental Component Summary

    The Medical Outcome Study SF-36 Mental Component Summary (MCS) is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

    Measured: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

  16. FACT-BMT Score

    The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.

    Measured: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

Timeline

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

  1. First posted20 Apr 2010 (estimated)
  2. Study startApr 2010
  3. Primary completion14 Feb 2017
  4. Study completionJun 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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01106833
Sponsor's protocol ID
BMTCTN0801
Other IDs
U01HL069294, BMT CTN 0801, U01HL06929406, 5U24CA076518
Status last verified
Nov 2018
First submitted
16 Apr 2010
Last updated
5 Dec 2018
Data monitoring committee
Yes
Individual data sharing
Yes: Findings will be published in a manuscript

Publications

  • Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

    PubMed 16338616

  • Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolanos-Meade J, Sarantopoulos S, Alousi AM, Abhyankar S, Waller EK, Mendizabal A, Zhu J, O'Brien KA, Lazaryan A, Wu J, Nemecek ER, Pavletic SZ, Cutler CS, Horowitz MM, Arora M; BMT CTN.. A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801. Haematologica. 2018 Nov;103(11):1915-1924. doi: 10.3324/haematol.2018.195123. Epub 2018 Jun 28.

    PubMed 29954931

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sirolimus + calcineurin inhibitor + prednisone and Sirolimus + prednisone in people with Chronic GVHD, run by Medical College of Wisconsin at 31 sites 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 4 inclusion and 14 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 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Proportion of Participants With Treatment Success (time frame: 6 months and 24 months post-randomization). 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 NCT01106833, which also lists 2 linked publications.

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 5 Dec 2018.

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