NCT00406393

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)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 304 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 2 Years – 60 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Leukemia, Myelocytic, Acute
• Leukemia, Lymphocytic, Acute
• Leukemia, Myeloid, Chronic
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	Tacrolimus	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.
DRUG	Methotrexate	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.
DRUG	Sirolimus	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.

Timeline

• Start date: 2006-11-01
• Primary completion: 2012-10-01
• Completion: 2015-10-01
• First posted: 2006-12-04
• Last updated: 2023-01-04
• Results posted: 2016-03-07

Locations

24 sites across 2 countries: United States, France