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

NCT01488253 | Terminated Phase 2 DMC

• 1 other identifier: KSBMT2011-01
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Hematopoietic stem cell transplantation; Graft vs Host disease; Prevention; Sirolimus; Tacrolimus

Outcome Measures

Primary Outcomes (1)

• The rate of grade II-IV acute graft-versus host disease

  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.

  100 days after allogeneic HSCT

Secondary Outcomes (7)

• The time to neutrophil and platelet engraftment

  within 6 weeks after transplant

• The incidence of grade III-IV acute GVHD

  During 100 days after transplant

• Non-relapse mortality

  During 100 days after transplant

• Mucositis severity

  100 days after transplant

• All infectious complications including CMV reactivation

  100 days after transplant

Study Arms (1)

acute GVHD prevention by sirolimus based regimen

EXPERIMENTAL

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.

Drug: Sirolimus; Drug: Tacrolimus

Interventions

Sirolimus DRUG

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.

Also known as: Rapamune (sirolimus, rapamycin)

acute GVHD prevention by sirolimus based regimen

Tacrolimus DRUG

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.

Also known as: Prograf (tacrolimus)

acute GVHD prevention by sirolimus based regimen

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Korean Society of Blood and Marrow Transplantation: lead
• Asan Medical Center: collaborator
• Chonbuk National University Hospital: collaborator
• Chonnam National University Hospital: collaborator
• Chung-Ang University Hosptial, Chung-Ang University College of Medicine: collaborator
• Daegu Catholic University Medical Center: collaborator
• Ewha Womans University Mokdong Hospital: collaborator
• Gachon University Gil Medical Center: collaborator
• Inha University Hospital: collaborator
• Inje University: collaborator
• Keimyung University Dongsan Medical Center: collaborator
• Korea University Anam Hospital: collaborator
• Pusan National University Hospital: collaborator
• Samsung Medical Center: collaborator
• Severance Hospital: collaborator
• Seoul St. Mary's Hospital: collaborator
• Seoul National University Hospital: collaborator
• Soonchunhyang University Hospital: collaborator

Study Sites (1)

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, 420-767, South Korea

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Graft vs Host Disease

Interventions

Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Seong Kyu Park, MD, PhD

  Clinical Trials Committee of The Korean Society of Blood and Marrow Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Trials Committee

Study Record Dates

• First Submitted: November 20, 2011
• First Posted: December 8, 2011
• Study Start: January 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2014
• Last Updated: April 3, 2015

Record last verified: 2015-03

Locations

KR (1)