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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Graft Versus Host Disease

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prograf + MTX<br> | Drug: Prograf<br>* Injection or oral<br>* Other names: Tacrolimus;Drug: Methotrexate<br>* Injection<br>|
| Active Comparator: Cyclosporine + MTX (historical control)<br> | Drug: Methotrexate<br>* Injection<br>Drug: Cyclosporine<br>* Injection or oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Day 1 up to Day 100 post-transplant | 
| 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 | 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). | Day 100 up to 1 year post-transplant | 
| Safety as assessed by adverse events |  | Day 1 up to 1 year post-transplant | 
| Safety as assessed by laboratory assessments | Includes hematology, biochemistry and trough plasma concentration analysis | Day 1 up to 1 year post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prograf, Graft versus host disease, Hematopoietic stem cell transplantation, Prophylaxis, Peripheral hematopoietic stem cell transplantation