Sirolimus/Tacrolimus Combination After HLA Matched Related Peripheral Blood Stem Cell Transplants
This study is currently recruiting participants.
Verified December 2011 by The Korean Society of Blood and Marrow Transplantation
Sponsor:
The Korean Society of Blood and Marrow Transplantation
Collaborators:
Asan Medical Center
Chonbuk National University Hospital
Chonnam National University Hospital
Chungang University Hospital
Daegu Catholic University Medical Center
Ewha Womans University
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 Bucheon 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
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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
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
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 Bucheon 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:
|
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Myelodysplastic Syndromes Preleukemia Acute Disease Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Disease Attributes |
Pathologic Processes Sirolimus Everolimus Tacrolimus Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on June 18, 2013