Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402)
Information source: Medical College of Wisconsin
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia, Myelocytic, Acute; Leukemia, Lymphocytic, Acute; Leukemia, Myeloid, Chronic; Myelodysplastic Syndromes
Intervention: Tacrolimus (Drug); Methotrexate (Drug); Sirolimus (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Medical College of Wisconsin Official(s) and/or principal investigator(s): Ryotaro Nakamura, MD, Principal Investigator, Affiliation: City of Hope National Medical Center Edward Ball, MD, Principal Investigator, Affiliation: UCSD Medical Center Laura Johnston, MD, Principal Investigator, Affiliation: Stanford Hospital and Clinics John Wingard, MD, Principal Investigator, Affiliation: University of Florida College of Medicine (Shands) Edmund Waller, MD, PhD, Principal Investigator, Affiliation: Emory University Jennifer E. Schwartz, MD, Principal Investigator, Affiliation: Indiana University School of Medicine Cory Cutler, MD, Study Chair, Affiliation: DFCI/Brigham & Women's Hospital Sung Choi, MD, Principal Investigator, Affiliation: University of Michigan William Hogan, MD, Principal Investigator, Affiliation: Mayo Clinic John DiPersio, MD, Principal Investigator, Affiliation: Washington University/Barnes Jewish Hospital Philip McCarthy, MD, Principal Investigator, Affiliation: Roswell Park Cancer Institute Hillard Lazarus, MD, Principal Investigator, Affiliation: University Hospitals of Cleveland/Case Western George Selby, MD, Principal Investigator, Affiliation: University of Oklahoma Medical Center David Porter, MD, Principal Investigator, Affiliation: University of Pennsylvania Paul Shaughnessy, MD, Principal Investigator, Affiliation: Texas Transplant Institute John McCarty, MD, Principal Investigator, Affiliation: Virginia Commonwealth University/MCV Hospital Walter Longo, MD, Principal Investigator, Affiliation: University of Wisconsin Hospital and Clinics Gwynn Long, MD, Principal Investigator, Affiliation: Duke University Nalini Janakiraman, MD, Principal Investigator, Affiliation: Henry Ford Health System Gerald Socie, MD, Principal Investigator, Affiliation: Hopital Saint-Louis Margarida Silverman, MD, Principal Investigator, Affiliation: University of Iowa Margaret MacMillan, MD, Principal Investigator, Affiliation: University of Minnesota - Clinical and Translational Science Institute Markus Mapara, MD, PHD, Principal Investigator, Affiliation: University of Pittsburgh
Summary
The study is designed as a phase III, randomized, open label, multicenter, prospective,
comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as
graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched,
related, peripheral blood stem cell transplantation in individuals with hematologic cancer.
Participants will be stratified by transplant center and will be randomly assigned to the
sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1: 1 ratio.
Clinical Details
Official title: 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)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Rate of Grades II-IV acute GVHD-free survival
Secondary outcome: Time to neutrophil engraftmentIncidence of acute GVHD Mucositis severity Time to discharge after transplant Infections Cytomegalovirus (CMV) reactivation and thrombotic microangiopathy Malignant disease relapse
Detailed description:
BACKGROUND:
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.
DESIGN NARRATIVE:
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.
Eligibility
Minimum age: 2 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Hopital Saint-Louis, Paris CEDEX 10, France
City of Hope National Medical Center, Duarte, California 91010, United States
UCSD Medical Center, LaJolla, California 92093, United States
Stanford Hospital and Clinics, Stanford, California 94305, United States
University of Florida College of Medicine (Shands), Gainesville, Florida 32610, United States
Emory University, Atlanta, Georgia 30322, United States
Indiana University Medical Center, Indianapolis, Indiana 46202, United States
University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242-1009, United States
DFCI/Brigham & Women's Hospital, Boston, Massachusetts 02114, United States
University of Michigan Medical Center, Ann Arbor, Michigan 48109-0914, United States
University of Minnesota, Minneapolis, Minnesota 55455, United States
Mayo Clinic, Rochester, Minnesota 55905, United States
Washington University/Barnes Jewish Hospital, St. Louis, Missouri 63110, United States
Roswell Park Cancer Institute, Buffalo, New York 14263, United States
Duke University Medical Center, Durham, North Carolina 27705, United States
University Hospitals of Cleveland/Case Western, Cleveland, Ohio 44106-5061, United States
Ohio State, Arthur G. James Cancer Hospital, Columbus, Ohio 43210, United States
University of Oklahoma Medical Center, Oklahoma City, Oklahoma 73104, United States
Oregon Health & Science University, Portland, Oregon 97239, United States
University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, United States
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, United States
Texas Transplant Institute, San Antonio, Texas 78229, United States
Virginia Commonwealth University/MCV Hospital, Richmond, Virginia 23298, United States
University of Wisconsin Hospital & Clinics, Madison, Wisconsin 53792-5156, United States
Additional Information
Blood and Marrow Transplant Clinical Trials Network
Starting date: November 2006
Last updated: May 20, 2015
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