To Demonstrate Superiority of Decitabine Over Azacitidine in Subjects With Intermediate- or High-risk MDS.

Study Overview
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Brief Summary
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The purpose of this study is to compare the response of patients with Intermediate or High Risk myelodysplastic syndromes (MDS) following treatment with decitabine or azacitidine.

Official Title
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A Randomized, Open-label, Parallel-Group Study Comparing the Efficacy and Safety of DACOGEN (Decitabine) for Injection and VIDAZA (Azacitidine) for Injection In Subjects With Intermediate or High Risk Myelodysplastic Syndromes (MDS)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: decitabine
* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects who meet all of the following criteria may be included in the study: Must have a diagnosis of primary myelodysplastic syndromes (MDS) of Intermediate-1 transfusion dependent, Intermediate-2, or High-risk [defined by International Prognostic Scoring System (IPSS) score of ≥0.5] and recognized French-American-British (FAB) classifications Male or female, 18 years of age or older with signed informed consent Adequate renal function Demonstrated normal liver function Female subjects of childbearing age must have negative pregnancy test within 1 week of study entry and agree to use adequate contraception for the duration of the trial and for a minimum of six months after last dose of decitabine or azacitidine received. Male subjects must agree to use adequate contraception for the duration of the trial and for a minimum of six months after last dose of decitabine or azacitidine received. Exclusion Criteria Subjects who meet any of the following criteria will be excluded from participation in the study: Current use of radiotherapy for extramedullary disease for 2 weeks prior to entering study (permitted if > 2 weeks from study entry and if recovered from toxic effects of therapy) Systemic fungal, bacterial, or viral infection which is not controlled (i.e., ongoing signs or symptoms of infection and without improvement despite appropriate treatment) Pregnancy or current lactation Significant concurrent disease, illness, or psychiatric disorder Treatment with an investigational agent 30 days prior to the first dose of decitabine or azacitidine

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: decitabine<br>* decitabine 20 mg/m^2 /day intravenous (IV) infusion for 5 days every 28 days<br>* Other names: Dacogen (decitabine);|
| Active Comparator: 2<br> | Drug: azacitidine<br>* azacitidine 75 mg/m^2 /day subcutaneous (SC) injection for 7 days every 28 days<br>* Other names: Vidaza (azacitidine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10^9/L; Neutrophils ≥ 1.0 X 10^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR. | 13 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10^9/L; Neutrophils ≥ 1.0 X 10^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR. | 36 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Myelodysplastic Syndromes