Anemia, Myelodysplastic Syndromes
Conditions
Keywords
MDS, Myelodysplastic syndromes, Anemia, Epoetin alfa, EPO
Brief summary
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
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.
Interventions
DRUGPlacebo
Matching volume 2 mLfor 48 weeks
DRUGEpoetin alfa
40,000 IU subcutaneously once every week (1 mL dose) for 48 weeks
Sponsors
Centocor Ortho Biotech Services, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Red Blood Cell (RBC) Transfusion | Approximately 48 weeks | Incidence of participants who received at least 1 Red Blood Cell (RBC) transfusion during the study (from randomization through the end of study) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RBC Transfusion From Day 29 Through the End of Study | Day 29 through the end of study (approximately 48 weeks) | incidence of participants who received at least 1 RBC transfusion from Day 29 through the end of study (approximately 48 weeks). |
| Transfusion Dependent | Approximately 48 weeks | Participants who were transfusion-dependent were those who received 4 or more RBC units during a consecutive 8-week period. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (1ml or 2 mL) subcutaneously once every week | 8 |
| Epoetin Alfa 40000 IU (1 mL) subcutaneously once every week | 8 |
| Epoetin Alfa 80000 IU (2 mL) subcutaneously once every week | 9 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study Closed Prematurely | 5 | 6 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Epoetin Alfa 40000 IU | Epoetin Alfa 80000 IU | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Age Continuous | 73 years STANDARD_DEVIATION 10.52 | 77.3 years STANDARD_DEVIATION 9.78 | 67.7 years STANDARD_DEVIATION 9.89 | 72.4 years STANDARD_DEVIATION 10.44 |
| Region of Enrollment CANADA | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment ITALY | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment RUSSIA | 2 participants | 0 participants | 4 participants | 6 participants |
| Region of Enrollment USA | 5 participants | 7 participants | 5 participants | 17 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 4 / 8 | 6 / 9 |
| serious Total, serious adverse events | 2 / 8 | 2 / 8 | 4 / 9 |
Outcome results
Primary
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)
Time frame: Approximately 48 weeks
Population: The intent-to-treat (ITT) population was defined as all participants randomly assigned to a treatment group, regardless of whether they received any treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Red Blood Cell (RBC) Transfusion | 5 participants |
| Epoetin Alfa 40000 IU | Red Blood Cell (RBC) Transfusion | 3 participants |
| Epoetin Alfa 80000 IU | Red Blood Cell (RBC) Transfusion | 1 participants |
Secondary
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).
Time frame: Day 29 through the end of study (approximately 48 weeks)
Population: The intent-to-treat (ITT) population was defined as all participants randomly assigned to a treatment group, regardless of whether they received any treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | RBC Transfusion From Day 29 Through the End of Study | 4 participants |
| Epoetin Alfa 40000 IU | RBC Transfusion From Day 29 Through the End of Study | 2 participants |
| Epoetin Alfa 80000 IU | RBC Transfusion From Day 29 Through the End of Study | 1 participants |
Secondary
Transfusion Dependent
Participants who were transfusion-dependent were those who received 4 or more RBC units during a consecutive 8-week period.
Time frame: Approximately 48 weeks
Population: The intent-to-treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Transfusion Dependent | 2 participants |
| Epoetin Alfa 40000 IU | Transfusion Dependent | 2 participants |
| Epoetin Alfa 80000 IU | Transfusion Dependent | 1 participants |