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A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease (GVHD) Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT CTN #0402)

Phase 3
2 Years
60 Years
Open (Enrolling)
Leukemia, Myelocytic, Acute, Leukemia, Lymphocytic, Acute, Leukemia, Myeloid, Chronic, Myelodysplastic Syndromes

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Trial Information

A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease (GVHD) Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT CTN #0402)


Stem cell transplantation is a standard therapy for acute and chronic leukemias and
myelodysplastic disorders. A common problem that may occur after a stem cell transplant is
a condition known as GVHD. The purpose of this study is to compare two combinations of
medications to see which is better at preventing GVHD. The combinations of medications in
this study are:

- Sirolimus and tacrolimus

- Methotrexate and tacrolimus

Doctors want to know if one combination is better than the other or if they both have the
same result.


Participants will receive one of the two conditioning regimens described in the protocol, at
the discretion of the transplant physician. The transplant physician must choose among these
regimens prior to the participant's assignment to the GVHD prophylaxis treatment.
Conditioning regimens will vary by center, but will be the same for all participants at each
center. Stem cell donors will donate peripheral blood stem cells according to local
institutional practices. Peripheral blood stem cells will not be manipulated or T-depleted
prior to administration. Standard post-transplant care will be administered. Participants
will be randomly assigned to one of two GVHD prophylaxis regimens and will be followed for
the endpoints of interest.

Participants will be followed for 114 days post-randomization for evaluation of the primary
endpoint, with additional follow-up for 2 years after transplantation for evaluation of
secondary endpoints.

Inclusion Criteria:

- 6/6 HLA-matched sibling, defined by Class I (HLA-A and B) serologic typing (or higher
resolution) and Class II (HLA-DRBI) molecular typing, who is willing to donate
peripheral blood stem cells, and meets institutional criteria for stem cell donation.
The donor must be medically eligible to donate stem cells, according to individual
transplant center criteria. Pediatric patients for whom a pediatric sibling donor is
not anticipated to be a suitable leukapheresis candidate are not eligible.

- Karnofsky performance status of at least 70% or Lansky performance status of at least
70% for participants less than 16 years old

- For participants less than 18 years old, willing and able to take oral medications,
per the treating physician's recommendations

Exclusion Criteria:

- Prior allogeneic or autologous transplant using any hematopoietic stem cell source

- Seropositive for the human immunodeficiency virus (HIV)

- Uncontrolled bacterial, viral, or fungal infection (currently taking medication and
progression of clinical symptoms)

- Pregnant (positive serum human chorionic gonadotropin [β-HCG] test) or breastfeeding
within 4 weeks of study entry

- Kidney function: serum creatinine outside the normal range for age, or measured
creatinine clearance less than 50 mL/min/1.72m^2 within 4 weeks of study entry

- Liver function: most recent direct bilirubin, ALT, or AST greater than two times the
upper limit of normal within 4 weeks of study entry

- Lung disease: in adults, FVC or FEV1 less than 60% of predicted value (corrected for
hemoglobin); in children, overt hypoxemia, as measured by an oxygen saturation of
less than 92% within 4 weeks of study entry

- Cardiac ejection fraction of less than 45% in adults and children, or less than 26%
shortening fraction in children within 4 weeks of study entry

- Cholesterol level greater than 500 mg/dL or triglyceride level greater than 500 mg/dL
while being treated, or not on appropriate lipid-lowering therapy within 4 weeks of
study entry

- Prior history of allergy to sirolimus

- Requires voriconazole at time of study entry

- Currently receiving another investigational drug unless cleared by the protocol
officer or protocol chair

- Participants with a history of cancer, other than resected basal cell carcinoma or
treated carcinoma in-situ. Cancer treated with curative intent for more than 5 years
previously will be allowed. Cancer treated with curative intent for less than 5
years previously will not be allowed unless approved by the protocol officer or
protocol chair.

Type of Study:


Study Design:

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

Outcome Measure:

Rate of Grades II-IV acute GVHD-free survival

Outcome Time Frame:

Day 114

Safety Issue:


Principal Investigator

Ryotaro Nakamura, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope National Medical Center


United States: Federal Government

Study ID:




Start Date:

November 2006

Completion Date:

October 2015

Related Keywords:

  • Leukemia, Myelocytic, Acute
  • Leukemia, Lymphocytic, Acute
  • Leukemia, Myeloid, Chronic
  • Myelodysplastic Syndromes
  • Acute Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Chronic Myelogenous Leukemia
  • Graft vs Host Disease
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia



Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
City of Hope National Medical Center Los Angeles, California  91010
University of Minnesota Minneapolis, Minnesota  55455
Oregon Health & Science University Portland, Oregon  97201
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 Wisconsin Hospital & Clinics Madison, Wisconsin  53792
Indiana University Medical Center Indianapolis, Indiana  46202
Texas Transplant Institute San Antonio, Texas  78229
UCSD Medical Center La Jolla, California  92093
Stanford Hospital and Clinics Stanford, California  94305
University of Florida College of Medicine (Shands) Gainesville, Florida  32610
Washington University/Barnes Jewish Hospital St. Louis, Missouri  63110
University Hospitals of Cleveland/Case Western Cleveland, Ohio  44106
University of Oklahoma Medical Center Oklahoma City, Oklahoma  73104
DFCI/Brigham & Women's Hospital Boston, Massachusetts  02114
Virginia Commonwealth University/MCV Hospital Richmond, Virginia  23298
Ohio State, Arthur G. James Cancer Hospital Columbus, Ohio  43210