Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease

Study Overview
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Brief Summary
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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.

Official Title
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Tacrolimus/Methotrexate Versus Cyclosporine/Methotrexate for Prophylaxis of Graft Versus Host Disease in Paediatric Patients

Conditions
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Graft vs Host Disease

Intervention / Treatment
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* Drug: Tacrolimus
* Drug: Cyclosporine
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus/Methotrexate<br>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 | Drug: Tacrolimus<br>* 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)<br>Drug: Methotrexate<br>* D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push<br>|
| Active Comparator: Cyclosporine/Methotrexate<br>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 | Drug: Cyclosporine<br>* 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)<br>Drug: Methotrexate<br>* D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | day 100 post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of infection | Fever would be categorized as fever occured before engraftment and after engraftment. If microbiologically documented, pathogen would be specified. | day 100 post transplantation | 
| 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 | day 100 post transplantation |