Sirolimus/Tacrolimus Combination After HLA Matched Related Peripheral Blood Stem Cell Transplants
Status:
Terminated
Trial end date:
2014-10-01
Target enrollment:
Participant gender:
Summary
Study Design: To evaluate the efficacy of the combination of sirolimus and tacrolimus as a
graft-versus-host disease prophylaxis, the investigators are going to perform a phase II,
multicenter clinical trial after human leukocyte antigen (HLA)-matched, related peripheral
blood stem cell transplants (PBSCT) in patients with hematologic malignancies. Total 116
patients will be accrued.
Objective: The primary objective is to evaluate the rates of 100 day Grade II-IV acute GVHD.
Secondary objectives include the time to neutrophil and platelet engraftment, the incidence
of grade III-IV acute GVHD, non-relapse mortality during 100 days after transplant, mucositis
severity, all infectious complications including cytomegalovirus (CMV) reactivation, vascular
complications (venoocclusive disease of liver; VOD, thrombotic microangiopathy; TMA),
disease-free survival, and overall survival at 1 year after transplant.
Eligibility Criteria: Eligible patients are between 20 and 60 years of age, have acute
leukemia, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and adequate
organ function. For available sibling donor, a serologic (or higher resolution) 6/6 Class I
HLA-A and B and molecular Class II DRB1 must be matched.
Treatment Description: Conditioning regimens will vary by center and donor will donate
peripheral blood stem cells according to local institutional practices. Peripheral blood stem
cells will not be manipulated or T-depleted prior to infusion. Tacrolimus will be
administered at 0.05 mg/kg/day intravenously by continuous infusion beginning on day -1 with
a target serum concentration of 5 to 10 ng/mL. Sirolimus will be administered as a 6 mg oral
loading dose on day -1, followed by a 3 mg/day single dose, with a target serum concentration
of 3 to 12 ng/mL. Levels will be monitored weekly during hospitalization and then as
clinically indicated. Intravenous tacrolimus will be converted to an oral equivalent dose
prior to discharge and both immunosuppressives will be tapered beginning at day +100 after
transplantation and eliminated by day +180 when clinically feasible.
Accrual Period: The estimated accrual period is three years. Patients will be followed for
100 days post transplantation for evaluation of the primary endpoint, with additional
follow-up to two years after transplantation for evaluation of secondary endpoints.
Phase:
Phase 2
Details
Lead Sponsor:
The Korean Society of Blood and Marrow Transplantation
Collaborators:
Asan Medical Center Chonbuk National University Hospital Chonnam National University Hospital Chung-Ang University Hosptial, Chung-Ang University College of Medicine Daegu Catholic University Medical Center Ewha Womans University Mokdong Hospital Gachon University Gil Medical Center Inha University Hospital Inje University Keimyung University Dongsan Medical Center Korea University Anam Hospital Pusan National University Hospital Samsung Medical Center Seoul National University Hospital Seoul St. Mary's Hospital Severance Hospital Soonchunhyang University Hospital