Comparison Between Cyclophosphamide and Combination of Methotrexate + Calcineurin Inhibitor for GVHD Prophylaxis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether cyclophosphamide post bone marrow transplant increases the rate of patients alive, in remission and without immunosuppression, one year after transplant, when compared with the combination of methotrexate and calcineurin inhibitor

Detailed Description
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We propose a study in which 150 patients will receive graft versus host disease prophylaxis with cyclophosphamide 50 mg/kg on day +3 and day +4 after bone marrow transplantation, and 150 patients will receive the usual combination of methotrexate and calcineurin inhibitor. The study was designed to last for 4 years. The primary endpoint is the rate of patients alive, in remission and without immunosuppression, one year after transplant. The assignment for each arm of the study will be done through simple randomization.

Official Title
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Randomized Study to Compare Post Bone Marrow Transplant Cyclophosphamide With the Combination of Methotrexate Plus Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Conditions
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Acute Myelogenous Leukemia, Acute Lymphoid Leukemia, Myeloproliferative Disease, Myelodysplastic Syndrome, Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia

Intervention / Treatment
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* Drug: ARM A Cyclophosphamide
* Drug: ARM B Calcineurin inhibitor and methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman 18 to 60 years of age. The patient should have a HLA matched donor The patient must need a bone marrow transplant for a malignant disease (Acute leukemia, myelodysplastic syndrome, myeloproliferative disease or myelodysplastic/myeloproliferative disease) Patients want to participate in the study, and able to give informed consent. Exclusion Criteria: Previous auto o allogeneic hematopoietic stem cell transplant Performance Status >2 (ECOG). Pregnancy HIV positive Active Infection Cardiac disease with ejection fraction < 45% Lung disease with FEV1, FVC ou DLCO <50% of predicted values. Renal Insufficiency with creatinine clearance < 60 ml/minute. Liver disease with bilirubin levels > twice the reference value or ALT or AST > three times the normal reference.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Graft versus host disease prophylaxis will be done with cyclophosphamide 50 mg/kg on day +3 and day +4 | Drug: ARM A Cyclophosphamide<br>* Cyclophosphamide 50 mg/kg on day+3 and day+4 after bone marrow transplantation<br>* Other names: Cyclophosphamide;|
| Active Comparator: Arm B<br>In this arm, patients will receive a combination of methotrexate and a calcineurin inhibitor as graft versus host disease prophylaxis | Drug: ARM B Calcineurin inhibitor and methotrexate<br>* Graft versus host disease prophylaxis will be done with the combination of a calcineurin inhibitor (either tacrolimus or cyclosporine) and methotrexate<br>* Other names: Calcineurin inhibitor and methotrexate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of patients alive, in remission and without immunosuppression, one year after bone marrow transplantation. | The rate of patients alive, in remission and without immunosuppression, one year after bone marrow transplantation. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of chronic graft versus host disease, one year after bone marrow transplantation | Cumulative incidence of chronic graft versus host disease, one year after bone marrow transplantation | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone marrow transplantation, graft versus host disease, Acute myelogenous leukemia, Acute lymphoid leukemia, Myeloproliferative disease, Myelodysplastic syndrome, Chronic myeloid leukemia, chronic myelomonocytic leukemia