Study to Assess the Safety and Efficacy of Tacrolimus (Prograf Capsule/Injection) and Methotrexate (MTX) Combination Therapy for Prevention of Graft Versus Host Disease (GVHD) in Patients Who Received Peripheral Hematopoietic Stem Cell Transplantation From a Sibling Donor

Sponsor

Astellas Pharma Korea, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02660684

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to assess the safety and efficacy of Tacrolimus (Prograf capsule, Prograf injection) and Methotrexate combination therapy for GVHD prophylaxis in patients who received peripheral hematopoietic stem cell transplantation from a sibling donor, and to compare with data from a historical control group that administered a conventional Cyclosporine formulation.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: Prograf Drug: Methotrexate Drug: Cyclosporine	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Historically-controlled, Multi-center Study to Assess the Safety and Efficacy of Tacrolimus (Prograf Capsule, Prograf Injection) and Methotrexate Combination Therapy for Prevention of GVHD in Patients Who Received Peripheral Hematopoietic Stem Cell Transplantation From a Sibling Donor

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prograf + MTX	Drug: Prograf Injection or oral Other Names: Tacrolimus Drug: Methotrexate Injection
Active Comparator: Cyclosporine + MTX (historical control)	Drug: Methotrexate Injection Drug: Cyclosporine Injection or oral

Arm

Intervention/Treatment

Experimental: Prograf + MTX

Drug: Prograf

Injection or oral

Other Names:

Tacrolimus

Drug: Methotrexate

Injection

Active Comparator: Cyclosporine + MTX (historical control)

Drug: Methotrexate

Injection

Drug: Cyclosporine

Injection or oral

Outcome Measures

Primary Outcome Measures

Number of occurrence sites of acute GVHD occurring within 100 days after peripheral hematopoietic stem cell transplantation from a sibling donor [Day 1 up to Day 100 post-transplant]
Severity of acute GVHD occurring within 100 days after peripheral hematopoietic stem cell transplantation from a sibling donor [Day 1 up to Day 100 post-transplant]
Severity is graded according to the Seattle criteria, between 1+ ~ 4+ depending on the severity of the injury of the skin, liver and digestive system, and the overall grade is classified by including the performance change.
Number of occurrence sites of chronic GVHD occurring after 100 days after peripheral hematopoietic stem cell transplantation from a sibling donor [Day 100 up to 1 year post-transplant]
Classification of chronic GVHD occurring after 100 days after peripheral hematopoietic stem cell transplantation from a sibling donor [Day 100 up to 1 year post-transplant]
Depending on the extent of occurrence, it is classified as limited (present only locally) and extensive (systemic lesions). Depending on the presence of preceding acute GVHD, it is classified as progressive for a patient with preceding acute GVHD (chronic GVHD following the occurrence of acute GVHD), quiescent (chronic GVHD after relief of acute GVHD symptoms) or otherwise (de novo).
Safety as assessed by adverse events [Day 1 up to 1 year post-transplant]
Safety as assessed by laboratory assessments [Day 1 up to 1 year post-transplant]
Includes hematology, biochemistry and trough plasma concentration analysis

Secondary Outcome Measures

Percentage of patients alive after peripheral hematopoietic stem cell transplantation from a sibling donor [Day 1 up to 1 year post-transplant]
Percentage of patients alive after peripheral hematopoietic stem cell transplantation from a sibling donor in comparison with Cyclosporine in combination with MTX [Day 1 up to 1 year post-transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Blood diseases for a standard risk group
Primary remission of AML (acute myeloid leukemia)
Primary remission of ALL (acute lymphocytic leukemia)
Secondary remission of ALL (acute lymphocytic leukemia)
SAA (severe aplastic anemia)
Chronic stage CML (chronic myeloid leukemia)
MDS (myelodysplastic syndrome)
Myeloma (multiple myeloma)
A patient who received peripheral hematopoietic stem cell transplantation from a HLA-matched sibling donor

Exclusion Criteria:

A patient with renal impairment (serum creatinine level ≥ 1.5mg/dl or 130μmol/l, GFR≤ 30%)
A pregnant or breastfeeding woman
A woman who is unwilling or unable to practice appropriate contraception during the study
A patient who is highly likely to experience aggravation during treatment due to active tuberculosis, other hepatic disease, hypertension, heart failure, chronic obstructive respiratory disease, etc.
A patient with hypersensitivity to tacrolimus