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

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

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.

Study Overview

• Status: Completed
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Drug: Tacrolimus; Drug: Methotrexate; Drug: Cyclosporine

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus/Methotrexate; 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; 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); Drug: Methotrexate; D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push
Active Comparator: Cyclosporine/Methotrexate; 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: Methotrexate; D1: 15mg/m2 iv push D3,6,(11): 10mg/m2 iv push; Drug: 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: JungMi Oh, Pharm.D, Seoul National University College of Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: November 25, 2012
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Methotrexate; Tacrolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: SNUCP_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO