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

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.

Conditions

• Acute Leukemia in Remission
• Myelodysplastic Syndromes
• Leukemia, Myeloid, Chronic-Phase
• Leukemia, Myeloid, Accelerated-Phase

Interventions

DRUG

Sirolimus

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.

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.

Sponsors & Collaborators

• Asan Medical Center

  collaborator OTHER

• Chonbuk National University Hospital

  collaborator OTHER

• Chonnam National University Hospital

  collaborator OTHER

• Chung-Ang University Hosptial, Chung-Ang University College of Medicine

  collaborator OTHER

• Daegu Catholic University Medical Center

  collaborator OTHER

• Ewha Womans University Mokdong Hospital

  collaborator OTHER

• Gachon University Gil Medical Center

  collaborator OTHER

• Inha University Hospital

  collaborator OTHER

• Inje University

  collaborator OTHER

• Keimyung University Dongsan Medical Center

  collaborator OTHER

• Korea University Anam Hospital

  collaborator OTHER

• Pusan National University Hospital

  collaborator OTHER

• Samsung Medical Center

  collaborator OTHER

• Severance Hospital

  collaborator OTHER

• Seoul St. Mary's Hospital

  collaborator OTHER

• Seoul National University Hospital

  collaborator OTHER

• Soonchunhyang University Hospital

  collaborator OTHER

• The Korean Society of Blood and Marrow Transplantation

  lead OTHER

Principal Investigators

• Seong Kyu Park, MD, PhD · Clinical Trials Committee of The Korean Society of Blood and Marrow Transplantation

Study Design

Allocation

NA

Purpose

PREVENTION

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2013-10-31

Completion

2014-10-31

Countries

• South Korea

Study Locations