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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 #0801)

Phase 2/Phase 3
Open (Enrolling)
Chronic GVHD

Thank you

Trial Information

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 #0801)

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.

Inclusion Criteria:

- 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 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

Exclusion Criteria:

- 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.

- 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: 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/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

- Known hypersensitivity to sirolimus.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase II: Proportion of subjects with CR/PR

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Paul Carpenter, MB, BS

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

April 2010

Completion Date:

March 2019

Related Keywords:

  • Chronic GVHD
  • Chronic Graft-versus-Host Disease (cGVHD)
  • Graft vs Host Disease



Johns Hopkins UniversityBaltimore, Maryland  21205
Roswell Park Cancer InstituteBuffalo, New York  14263
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Medical College of WisconsinMilwaukee, Wisconsin  53226
Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224
Rush University Medical CenterChicago, Illinois  60612-3824
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
All Children's HospitalSt. Petersburg, Florida  33701
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Mount Sinai Medical CenterNew York, New York  10029
City of Hope National Medical CenterLos Angeles, California  91010
University of MinnesotaMinneapolis, Minnesota  55455
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Duke University Medical CenterDurham, North Carolina  27710
University of Michigan Medical CenterAnn Arbor, Michigan  48104-0914
Emory UniversityAtlanta, Georgia  30322
University of ChicagoChicago, Illinois  60637
Texas Transplant InstituteSan Antonio, Texas  78229
Children's Healthcare of AtlantaAtlanta, Georgia  30342
Stanford Hospital and ClinicsStanford, California  94305
University of Florida College of Medicine (Shands)Gainesville, Florida  32610
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
University of Texas/MD Anderson CRCHouston, Texas  77030
Utah BMT/Primary Children's Medical CenterSalt Lake City, Utah  84132
University of Kansas HospitalKansas City, Kansas  66160
DFCI/Brigham & Women'sBoston, Massachusetts  02114
University of Oklahoma Medical CenterOklahoma City, Oklahoma  73104
Cook Children's Medical CenterFort Worth, Texas  76104
University of North Carolina Hospital at Chapel HillChapel Hill, North Carolina  27599
University of Maryland, Greenbaum Cancer CenterBaltimore, Maryland  21201
West Virginia University HospitalMorgantown, West Virginia  26506-9162
Karmanos Cancer Institute/Children's Hospital of MichiganDetroit, Michigan  48201
University of California San Diego Medical CenterSan Diego, California  92103-8409
Washington University, Barnes Jewish HospitalSt. Louis, Missouri  63110
Blood & Marrow Transplant Program at Northside HospitalAtlanta, Georgia  30342
Indiana University Medical Center/Riley HospitalIndianapolis, Indiana  46202
University of Louisville/Kosair Children's HospitalLouisville, Kentucky  40202
St. Louis Children's Hospital, Washington UniversitySt. Louis, Missouri  63110
Cohen (Schneider) Children's HospitalNew Hyde Park, New York  11040
Mayo ClinicRochester, New York  55905
Jewish Hospital BMT ProgramCincinnati, Ohio  45236
University Hospitals of Cleveland/ Case WesternCleveland, Ohio  44106-5061
Oregon Health & Science University (A) and (P)Portland, Oregon  97239-3098
Fox Chase, Temple University BMT ProgramPhiladelphia, Pennsylvania  19111-2442
Virginia Commonwealth University/MCV HospitalsRichmond, Virginia  23298
Arizona Canter Center, University of ArizonaTucson, Arizona  85724-5024
University of Massachusetts/Memorial Medical CenterWorcester, Massachusetts  01655