Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents

Amgen

Status and phase: Completed; Phase 2

Conditions: Thrombocytopenia; MDS; Myelodysplastic Syndromes

Treatments: Drug: Placebo; Biological: AMG 531 (Romiplostim); Drug: Decitabine; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00321711

20050232

Details and patient eligibility

About

The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.

Enrollment: 69 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: - Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification - Low, Intermediate-1 or Intermediate-2 risk category MDS using the IPSS (International Prognostic Scoring System) - Planned to receive either azacytidine 75 mg/m2 by subcutaneous administration each day for 7 days or decitabine 20 mg/m2 by intravenous administration each day for 5 days for at least 4 cycles Exclusion Criteria:

• Prior exposure to >3 cycles hypomethylating agents
• Prior history of leukemia or aplastic anemia
• Prior history of bone marrow transplantation
• Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ³ 3 years before randomization
• Active or uncontrolled infections
• Unstable angina, congestive heart failure [NYHA (New York Heart Association) > class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
• History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past year
• History of venous thrombosis that currently requires anti-coagulation therapy
• Received IL-11 within 4 weeks of screening
• Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
• Have previously received any other thrombopoietic growth factor

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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69 participants in 5 patient groups, including a placebo group

Dose level 1 500 AMG 531 (Part A - azacitidine)

Active Comparator group

Description:

500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

Treatment:

Biological: AMG 531 (Romiplostim)

Drug: Azacitidine

Dose level 1 750 AMG 531 (Part B - decitabine)

Active Comparator group

Description:

750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles

Treatment:

Biological: AMG 531 (Romiplostim)

Drug: Decitabine

Dose level 2 750 AMG 531 (Part A - azacitidine)

Active Comparator group

Description:

750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

Treatment:

Biological: AMG 531 (Romiplostim)

Drug: Azacitidine

Placebo (Part A - azacitidine)

Placebo Comparator group

Description:

Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

Treatment:

Drug: Azacitidine

Drug: Placebo

Placebo (Part B - decitabine)

Placebo Comparator group

Description:

Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles

Treatment:

Drug: Placebo

Drug: Decitabine