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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 engraftment

Incidence 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

Page last updated: August 23, 2015

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