Sirolimus/Tacrolimus Combination After HLA Matched Related Peripheral Blood Stem Cell Transplants
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.
Acute Leukemia in Remission
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Accelerated-Phase
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Multicenter Trials to Evaluate the Efficacy and Toxicity of Sirolimus/Tacrolimus Combination as a GVHD Prophylaxis After HLA Matched Related PBSCT|
- The rate of grade II-IV acute graft-versus host disease [ Time Frame: 100 days after allogeneic HSCT ] [ Designated as safety issue: Yes ]Patients will be followed for 100 days post transplantation for evaluation of the primary endpoint (the incidence and severity of acute GVHD) and clinical data will be collected at 100 day after HSCT using case report form. Acute GVHD will be graded according to the consensus grading scale.
- The time to neutrophil and platelet engraftment [ Time Frame: within 6 weeks after transplant ] [ Designated as safety issue: Yes ]The time of engraftment is defined as the first of three consecutive days on which the absolute neutrophil counts exceed 0.5 X 10(9)/L and platelet count to 20 X 10(9)/L, respectively.
- The incidence of grade III-IV acute GVHD [ Time Frame: During 100 days after transplant ] [ Designated as safety issue: Yes ]Acute GVHD will be graded according to the consensus grading scale.
- Non-relapse mortality [ Time Frame: During 100 days after transplant ] [ Designated as safety issue: Yes ]All deaths without relapse or progression of underlying disease
- Mucositis severity [ Time Frame: 100 days after transplant ] [ Designated as safety issue: Yes ]It will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0).
- All infectious complications including CMV reactivation [ Time Frame: 100 days after transplant ] [ Designated as safety issue: Yes ]The incidence and type of infectious complications
- Vascular complications [ Time Frame: 100 days after transplant ] [ Designated as safety issue: Yes ]The incidence of venoocclusive disease of liver and syndrome of thrombotic microangiopathy.
- Clinical outcome at 1 year after transplant [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]Disease-free survival and overall survival at 1 year after transplant
|Study Start Date:||January 2012|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: acute GVHD prevention by sirolimus based regimen
The investigators will evaluated the primary endpoint and secondary endpoints comparing with historical control, that is used tacrolimus/methotrexate as a GVHD prophylaxis after HLA-matched, related PBSCT.
Sirolimus will be administered as a 6-mg oral loading dose beginning on day -1, followed by 3 mg per day orally in a single morning dose with a target trough level of 5-12 ng/mL. Trough levels will be measured once a week. Sirolimus will be gradually tapered beginning at day +100, and eliminated by day +180, unless the patient required continued treatment for GVHD or experienced toxicity related to drugs.
Other Name: Rapamune (sirolimus, rapamycin)Drug: Tacrolimus
Tacrolimus will be administered beginning on day -1 at 0.05 mg/kg intravenously by continuous infusion every 24 hours, with a target serum level of 5 to 10 ng/mL. Tacrolimus dosing is converted to oral capsules prior to discharge. Trough levels will be measured once a week. Tacrolimus will be gradually tapered beginning at day +100, and eliminated by day +180, unless the patient required continued treatment for GVHD or experienced toxicity related to drugs.
Other Name: Prograf (tacrolimus)
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488253
|Korea, Republic of|
|Soonchunhyang University Bucheon Hospital|
|Bucheon, Gyeonggi, Korea, Republic of, 420-767|
|Principal Investigator:||Seong Kyu Park, MD, PhD||Clinical Trials Committee of The Korean Society of Blood and Marrow Transplantation|