A Study Evaluating Epoetin Alfa 40,000 IU (International Units) Every Week or 80,000 IU Every Week Compared to Placebo in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes at Risk for Transfusion

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that Epoetin alfa treatment reduces red blood cell transfusions in anemic patients with myelodysplastic syndromes (MDS). Myelodysplastic syndromes are a group of disorders characterized by progressive bone marrow failure and an increased risk of development of leukemia.

Detailed Description
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This is a randomized (patients are assigned by chance to a treatment group), double-blind (neither the patient or the physician know which treatment is being received by the patient), placebo-controlled, multicenter study of epoetin alfa in anemic patients who are diagnosed with myelodysplastic syndromes (MDS) according to protocol-specified criteria. Patients meeting entry criteria for the study will be randomly assigned to receive epoetin alfa 40,000 IU or 80,000 IU or a matching volume of placebo administered by subcutaneous (under the skin) injection once every week. Doses of study drug will be withheld, decreased, or increased on the basis of weekly hemoglobin concentrations monitored in patients and predefined dose adjustment guidelines. An Independent Data Monitoring Committee (IDMC) will periodically review study data and for the assessment of disease progression, an independent central reviewer will review bone marrow specimens and peripheral blood counts. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by physical examination, laboratory tests and evaluation of adverse events. Patients in the Treatment Phase will be randomly assigned to receive once weekly epoetin alfa subcutaneously (SC) at a dose of 40,000 IU (1 mL) or 80,000 IU (2ML) or matching volume of placebo (1 mL or 2 mL) once every week for 48 weeks. Patients may continue to receive double-blinded treatment after 48-weeks.

Official Title
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A Randomized, Double Blind, Placebo Controlled, Multicenter Study Evaluating Epoetin Alfa Initiated at 40,000 IU Every Week or 80,000 IU Every Week Versus Placebo in Subjects With IPSS Low- or Intermediate-1 Risk Myelodysplastic Syndromes at Risk For Transfusion

Conditions
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Myelodysplastic Syndromes, Anemia

Intervention / Treatment
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* Drug: Placebo
* Drug: Epoetin alfa
* Drug: Placebo
* Drug: Epoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MDS according to protocol-specified criteria via bone marrow studies performed within 12 weeks before randomization Exclusion Criteria: No prior or concurrent treatment with epoetin alfa or any other approved or experimental erythropoietin stimulating agents (ESAs) within the previous 12 months before randomization No prior use of approved or experimental agents for the treatment of MDS or recent treatment with granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) for the treatment of neutropenia Patients must not have secondary MDS or anemia caused by factors other than MDS (including iron deficiency, vitamin B12 or folate deficiencies, hemolysis, chronic renal failure, or gastrointestinal bleeding) No history (within 12 months) of deep venous thrombosis or history (within 6 months) of stroke, acute coronary syndrome or other arterial thrombosis Not currently receiving therapeutic anticoagulants or have uncontrolled hypertension No uncontrolled disease or dysfunction deemed clinically significant by the Investigator not attributable to MDS

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Epoetin alfa 40 000 IU subcutaneously once every week (1 mL dose) for 48 weeks | Drug: Epoetin alfa<br>* 40,000 IU subcutaneously once every week (1 mL dose) for 48 weeks<br>|
| Experimental: 002<br>Epoetin alfa 80 000 IU subcutaneously once every week (2 mL dose) for 48 weeks | Drug: Epoetin alfa<br>* 80,000 IU subcutaneously once every week (2 mL dose) for 48 weeks<br>|
| Placebo Comparator: 003<br>Placebo Matching volume 1 mL for 48 weeks | Drug: Placebo<br>* Matching volume 1 mL for 48 weeks<br>|
| Placebo Comparator: 004<br>Placebo Matching volume 2 mLfor 48 weeks | Drug: Placebo<br>* Matching volume 2 mLfor 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red Blood Cell (RBC) Transfusion | Incidence of participants who received at least 1 Red Blood Cell (RBC) transfusion during the study (from randomization through the end of study) | Approximately 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC Transfusion From Day 29 Through the End of Study | incidence of participants who received at least 1 RBC transfusion from Day 29 through the end of study (approximately 48 weeks). | Day 29 through the end of study (approximately 48 weeks) | 
| Transfusion Dependent | Participants who were transfusion-dependent were those who received 4 or more RBC units during a consecutive 8-week period. | Approximately 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Myelodysplastic syndromes, Anemia, Epoetin alfa, EPO