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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 University Baltimore, Maryland  21205
Roswell Park Cancer Institute Buffalo, New York  14263
Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
Medical University of South Carolina Charleston, South Carolina  29425-0721
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Medical College of Wisconsin Milwaukee, Wisconsin  53226
Western Pennsylvania Hospital Pittsburgh, Pennsylvania  15224
Rush University Medical Center Chicago, Illinois  60612-3824
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Hackensack University Medical Center Hackensack, New Jersey  07601
All Children's Hospital St. Petersburg, Florida  33701
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Mount Sinai Medical Center New York, New York  10029
City of Hope National Medical Center Los Angeles, California  91010
University of Minnesota Minneapolis, Minnesota  55455
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Duke University Medical Center Durham, North Carolina  27710
University of Michigan Medical Center Ann Arbor, Michigan  48104-0914
Emory University Atlanta, Georgia  30322
University of Chicago Chicago, Illinois  60637
Texas Transplant Institute San Antonio, Texas  78229
Children's Healthcare of Atlanta Atlanta, Georgia  30342
Stanford Hospital and Clinics Stanford, California  94305
University of Florida College of Medicine (Shands) Gainesville, Florida  32610
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
University of Texas/MD Anderson CRC Houston, Texas  77030
Utah BMT/Primary Children's Medical Center Salt Lake City, Utah  84132
University of Kansas Hospital Kansas City, Kansas  66160
DFCI/Brigham & Women's Boston, Massachusetts  02114
University of Oklahoma Medical Center Oklahoma City, Oklahoma  73104
Cook Children's Medical Center Fort Worth, Texas  76104
University of North Carolina Hospital at Chapel Hill Chapel Hill, North Carolina  27599
University of Maryland, Greenbaum Cancer Center Baltimore, Maryland  21201
West Virginia University Hospital Morgantown, West Virginia  26506-9162
Karmanos Cancer Institute/Children's Hospital of Michigan Detroit, Michigan  48201
University of California San Diego Medical Center San Diego, California  92103-8409
Washington University, Barnes Jewish Hospital St. Louis, Missouri  63110
Blood & Marrow Transplant Program at Northside Hospital Atlanta, Georgia  30342
Indiana University Medical Center/Riley Hospital Indianapolis, Indiana  46202
University of Louisville/Kosair Children's Hospital Louisville, Kentucky  40202
St. Louis Children's Hospital, Washington University St. Louis, Missouri  63110
Cohen (Schneider) Children's Hospital New Hyde Park, New York  11040
Mayo Clinic Rochester, New York  55905
Jewish Hospital BMT Program Cincinnati, Ohio  45236
University Hospitals of Cleveland/ Case Western Cleveland, Ohio  44106-5061
Oregon Health & Science University (A) and (P) Portland, Oregon  97239-3098
Fox Chase, Temple University BMT Program Philadelphia, Pennsylvania  19111-2442
Virginia Commonwealth University/MCV Hospitals Richmond, Virginia  23298
Arizona Canter Center, University of Arizona Tucson, Arizona  85724-5024
University of Massachusetts/Memorial Medical Center Worcester, Massachusetts  01655