Sirolimus/Tacrolimus Combination After HLA Matched Related Peripheral Blood Stem Cell Transplants

• Status: Terminated
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

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
• Treatments: Everolimus; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

• Ability to provide written informed consent prior to participating to the study

• Patients with acute leukemia in remission, MDS, and CML in chronic & accelerated phase

• Patients with HLA identical donor, a serologic (or higher resolution) 6/6 Class I HLA-A and B and molecular Class II DRB1 must be matched.

• Patients with an ECOG performance status score < 2

• Adequate end organ functions as defined by: Total bilirubin < 1.5 × ULN, AST and ALT < 2.5 × ULN, Creatinine < 1.5 × ULN.

• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug.

Exclusion Criteria:

• Acute promyelocytic leukemia (M3)

• Patients with another primary malignancy other than hematologic disease

• Patients with a severe or uncontrolled medical condition (i.e. uncontrolled diabetes, chronic renal disease)

• Patients who are ① pregnancy, ② breast feeding, ③ of childbearing potential without a negative pregnancy test prior to baseline and ④ male or female of childbearing potential unwilling to use barrier contraceptive precautious throughout the trial (post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential)

• Patients with an ECOG performance status score ≥ 2

• Patients with known positivity for HIV; baseline testing for HIV is not required