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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2011 by The Korean Society of Blood and Marrow Transplantation
Sponsor:
Collaborators:
Asan Medical Center
Chonbuk National University Hospital
Chonnam National University Hospital
Chungang University Hospital
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
Severance Hospital
Seoul St. Mary's Hospital
Seoul National University Hospital
Soonchunhyang University Hospital
Information provided by (Responsible Party):
Seong Kyu Park, MD, The Korean Society of Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT01488253
First received: November 20, 2011
Last updated: August 16, 2012
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Acute Leukemia in Remission
Myelodysplastic Syndromes
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Accelerated-Phase
Drug: Sirolimus
Drug: Tacrolimus
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by The Korean Society of Blood and Marrow Transplantation:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 116
Study Start Date: January 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488253

Contacts
Contact: Ji Yeon Kim, RN 82-32-621-5191 banji79@schmc.ac.kr
Contact: Mi Sun Jeong, RN 82-32-621-5191 jms9553@hanmail.net

Locations
Korea, Republic of
Soonchunhyang University Bucheon Hospital Recruiting
Bucheon, Gyeonggi, Korea, Republic of, 420-767
Contact: Ji Yeon Kim, RN    82-32-621-5191    banji79@schmc.ac.kr   
Sub-Investigator: Hee Je Kim, MD, PhD         
Sub-Investigator: Jin Seok Kim, MD         
Sub-Investigator: Dae Sik Hong, MD, PhD         
Sub-Investigator: Se Hyung Kim, MD         
Sub-Investigator: Jina Yun, MD         
Sub-Investigator: Jong Ho Won, MD, PhD         
Sub-Investigator: Deok Hwan Yang, MD, PhD         
Sub-Investigator: Sung Hyun Kim, MD, PhD         
Sub-Investigator: Seok Lee, MD, PhD         
Sub-Investigator: Jae Yong Kwak, MD, PhD         
Sub-Investigator: Jeong A Kim, MD, PhD         
Sponsors and Collaborators
The Korean Society of Blood and Marrow Transplantation
Asan Medical Center
Chonbuk National University Hospital
Chonnam National University Hospital
Chungang University Hospital
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
Severance Hospital
Seoul St. Mary's Hospital
Seoul National University Hospital
Soonchunhyang University Hospital
Investigators
Principal Investigator: Seong Kyu Park, MD, PhD Clinical Trials Committee of The Korean Society of Blood and Marrow Transplantation
  More Information

No publications provided

Responsible Party: Seong Kyu Park, MD, Director of Clinical Trials Committee, The Korean Society of Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT01488253     History of Changes
Other Study ID Numbers: KSBMT2011-01
Study First Received: November 20, 2011
Last Updated: August 16, 2012
Health Authority: Korea: Institutional Review Board
Korea: Food and Drug Administration

Keywords provided by The Korean Society of Blood and Marrow Transplantation:
Hematopoietic stem cell transplantation
Graft vs Host disease
Prevention
Sirolimus
Tacrolimus

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Acute Disease
Leukemia, Myeloid, Accelerated Phase
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Myeloproliferative Disorders
Disease Attributes
Pathologic Processes
Tacrolimus
Sirolimus
Everolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on October 01, 2014