Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402)
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)
4 other identifiers
interventional
304
2 countries
24
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2006
Longer than P75 for phase_3
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2006
CompletedFirst Submitted
Initial submission to the registry
November 30, 2006
CompletedFirst Posted
Study publicly available on registry
December 4, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedResults Posted
Study results publicly available
March 7, 2016
CompletedJanuary 4, 2023
December 1, 2022
5.9 years
November 30, 2006
January 6, 2016
December 7, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Grades II-IV Acute GVHD-free Survival
The primary objective is to compare rates of 114-day Grades II-IV acute GVHD-free survival post randomization for HLA-matched, related donor allogeneic peripheral blood stem cell transplantation using two different GVHD prophylaxis regimens. Participants are graded on a scale of 1 to 4 according to their symptoms and organs involved, where 4 represents a worse grade.
Day 114
Secondary Outcomes (11)
Incidence of Acute GVHD
Measured at Day 100
Time to Neutrophil and Platelet Engraftment
Measured through Day 100
Mucositis Severity
Measured at Day 21
Rate of Veno-occlusive Disease (VOD)
Measured through Day 100
Thrombotic Microangiopathy (TMA) Infection
Measured through Day 100
- +6 more secondary outcomes
Study Arms (2)
Tacrolimus/Methotrexate
ACTIVE COMPARATORPatients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Tacrolimus/Sirolimus
EXPERIMENTALPatients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.
Interventions
Adults and Children: Tacrolimus will be given at a dose of 0.02 mg/kg every 24 hours as a continuous intravenous infusion beginning on Day -3. An effort will be made to convert the tacrolimus to oral dosing at 2-3 times the total 24-hour intravenous dose, split into 2 doses given every 12 hours as soon as clinically feasible. The target serum level for tacrolimus is 5-10 ng/mL.
Methotrexate will be given at a dose of 15 mg/m2 on Day 1 after transplantation, and at a dose of 10 mg/m2 on Days 3, 6 and 11 after transplantation.
Adults: Sirolimus will be given in a loading dose of 12 mg on Day -3 followed by a daily oral dose of 4 mg per day. Doses may be repeated if the subject vomits within 15 minutes of an oral dose. Children: Children aged \< 12.0 years OR weighing \< 40.0 kg will be given an oral loading dose of sirolimus of 3 mg/m2 followed by a daily oral dose of 1 mg/m2, rounded to the nearest full milligram. The target serum level for sirolimus is 3-12 ng/mL.
Eligibility Criteria
You may qualify if:
- /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
You may not qualify if:
- 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, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) greater than two times the upper limit of normal within 4 weeks of study entry
- Lung disease: in adults, forced vital capacity (FVC) or forced expiratory volume in one second (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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical College of Wisconsinlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (24)
City of Hope National Medical Center
Duarte, California, 91010, United States
UCSD Medical Center
La Jolla, 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
Hopital Saint-Louis
Paris, CEDEX 10, France
Related Publications (1)
Cutler C, Logan B, Nakamura R, Johnston L, Choi S, Porter D, Hogan WJ, Pasquini M, MacMillan ML, Hsu JW, Waller EK, Grupp S, McCarthy P, Wu J, Hu ZH, Carter SL, Horowitz MM, Antin JH. Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood. 2014 Aug 21;124(8):1372-7. doi: 10.1182/blood-2014-04-567164. Epub 2014 Jun 30.
PMID: 24982504RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Corporation
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 30, 2006
First Posted
December 4, 2006
Study Start
November 1, 2006
Primary Completion
October 1, 2012
Study Completion
October 1, 2015
Last Updated
January 4, 2023
Results First Posted
March 7, 2016
Record last verified: 2022-12
Data Sharing
- IPD Sharing
- Will share
Findings will be published in a manuscript.