Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease
Primary Purpose
Graft vs Host Disease
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Tacrolimus
Cyclosporine
Methotrexate
Sponsored by
About this trial
This is an interventional prevention trial for Graft vs Host Disease
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of hematological malignancy
- Age under 18 years old
- Serum bilirubin less than 1.5 X upper limit of normal
- Aspartate transaminase, Alanine transaminase less than 2.5 X upper limit of normal
- Alkaline phosphatase less than 2.5 X upper limit of normal
- Serum creatinine less than 1.5 X upper limit of normal
- Agrees to participate, and informed consent signed
Exclusion Criteria:
- Evidence of HIV infection
- Documented uncontrolled disease (infections)
- Prior transplantation (hematopoietic stem cell or solid organs)
Sites / Locations
- Asan Medical Center
- Samsung Medical Center
- Seoul National University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tacrolimus/Methotrexate
Cyclosporine/Methotrexate
Arm Description
Tacrolimus D-1~D20: iv infusion, q24hr (first daily dose: 0.03mg/kg) D20~D100: po q12hr (first daily dose: the quadruple of last iv dose) Dose modification according to therapeutic drug monitoring(TDM) (10-20ng/ml) Methotrexate D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Cyclosporine D-1~D20: iv infusion, q24hr (first daily dose: 3mg/kg) D20~D100: po q12hr (first daily dose: the 3 times of last iv dose) Dose modification according to TDM (200-300ng/ml) Methotrexate D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Outcomes
Primary Outcome Measures
incidence of grade II-IV acute graft versus host disease
Overall grade I graft-versus-host disease denoted stage 1 to 2 skin involvement with no liver or gut involvement. Overall grade II graft-versus-host disease denoted stage 3 skin involvement or stage 1 liver or gut involvement. Overall grade III graft-versus-host disease denoted stage 4 skin involvement or stage 2 to 4 liver or gut involvement without graft-versus-host disease as a major contributing cause of death. And Overall grade IV graft-versus-host disease denoted stage 4 skin involvement or stage 2 to 4 liver or gut involvement with graft-versus-host disease as a major contributing cause of death.
Secondary Outcome Measures
incidence of infection
Fever would be categorized as fever occured before engraftment and after engraftment. If microbiologically documented, pathogen would be specified.
incidence of adverse drug reactions
adverse drug reactions would be measured by Common Terminology Criteria for Adverse Events v3. And for determinating the likelihood of whether an adverse drug reaction is actually due to the drug, Naranjo algorithm would be used
Full Information
NCT ID
NCT01788501
First Posted
November 25, 2012
Last Updated
March 20, 2017
Sponsor
Seoul National University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01788501
Brief Title
Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease
Official Title
Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease in Paediatric Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
November 2011 (Actual)
Primary Completion Date
March 1, 2017 (Actual)
Study Completion Date
March 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to compare efficacy and safety of tacrolimus/methotrexate with cyclosporine/methotrexate for graft versus host disease prophylaxis in paediatric allogeneic hematopoietic stem cell transplantation patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs Host Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tacrolimus/Methotrexate
Arm Type
Experimental
Arm Description
Tacrolimus D-1~D20: iv infusion, q24hr (first daily dose: 0.03mg/kg) D20~D100: po q12hr (first daily dose: the quadruple of last iv dose) Dose modification according to therapeutic drug monitoring(TDM) (10-20ng/ml)
Methotrexate D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Arm Title
Cyclosporine/Methotrexate
Arm Type
Active Comparator
Arm Description
Cyclosporine D-1~D20: iv infusion, q24hr (first daily dose: 3mg/kg) D20~D100: po q12hr (first daily dose: the 3 times of last iv dose) Dose modification according to TDM (200-300ng/ml)
Methotrexate D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
D-1~D20: iv infusion, q24hr (first daily dose: 0.03mg/kg) D20~D100: po q12hr (first daily dose: the quadruple of last iv dose) Dose modification according to TDM (10-20ng/ml)
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Intervention Description
D-1~D20: iv infusion, q24hr (first daily dose: 3mg/kg) D20~D100: po q12hr (first daily dose: the 3 times of last iv dose) Dose modification according to TDM (200-300ng/ml)
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Primary Outcome Measure Information:
Title
incidence of grade II-IV acute graft versus host disease
Description
Overall grade I graft-versus-host disease denoted stage 1 to 2 skin involvement with no liver or gut involvement. Overall grade II graft-versus-host disease denoted stage 3 skin involvement or stage 1 liver or gut involvement. Overall grade III graft-versus-host disease denoted stage 4 skin involvement or stage 2 to 4 liver or gut involvement without graft-versus-host disease as a major contributing cause of death. And Overall grade IV graft-versus-host disease denoted stage 4 skin involvement or stage 2 to 4 liver or gut involvement with graft-versus-host disease as a major contributing cause of death.
Time Frame
day 100 post transplantation
Secondary Outcome Measure Information:
Title
incidence of infection
Description
Fever would be categorized as fever occured before engraftment and after engraftment. If microbiologically documented, pathogen would be specified.
Time Frame
day 100 post transplantation
Title
incidence of adverse drug reactions
Description
adverse drug reactions would be measured by Common Terminology Criteria for Adverse Events v3. And for determinating the likelihood of whether an adverse drug reaction is actually due to the drug, Naranjo algorithm would be used
Time Frame
day 100 post transplantation
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of hematological malignancy
Age under 18 years old
Serum bilirubin less than 1.5 X upper limit of normal
Aspartate transaminase, Alanine transaminase less than 2.5 X upper limit of normal
Alkaline phosphatase less than 2.5 X upper limit of normal
Serum creatinine less than 1.5 X upper limit of normal
Agrees to participate, and informed consent signed
Exclusion Criteria:
Evidence of HIV infection
Documented uncontrolled disease (infections)
Prior transplantation (hematopoietic stem cell or solid organs)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JungMi Oh, Pharm.D
Organizational Affiliation
Seoul National University College of Pharmacy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease
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