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

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Anemia
• Intervention / Treatment: Drug: Epoetin alfa; Drug: Epoetin alfa; Drug: Placebo; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Centocor Ortho Biotech Services, L.L.C.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: June 5, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimate): June 11, 2008

Study Record Updates

• Last Update Posted (Estimate): October 5, 2012
• Last Update Submitted That Met QC Criteria: October 2, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Anemia; Epoetin alfa; MDS; EPO; Myelodysplastic syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: CR013651; EPOANE3018