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

Phase 2

Completed

• Conditions: MDS; Thrombocytopenia; Myelodysplastic Syndromes
• Interventions: Biological: AMG 531 (Romiplostim); Drug: Placebo; Drug: Azacitidine; Drug: Decitabine

• Registration Number: NCT00321711
• Lead Sponsor: Amgen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-05-02
• Study First Submitted QC: 2006-05-02
• Study First Posted: 2006-05-04
• Study Start: 2006-10-01
• Primary Completion: 2009-10-19
• Study Completion: 2009-10-19
• Results First Submitted: 2010-11-18
• Results First Submitted QC: 2011-03-03
• Results First Posted: 2011-04-05
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-20
• Last Update Posted: 2018-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose level 1 750 AMG 531 (Part B - decitabine)	AMG 531 (Romiplostim)	750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles
Dose level 2 750 AMG 531 (Part A - azacitidine)	AMG 531 (Romiplostim)	750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Placebo (Part A - azacitidine)	Placebo	Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Dose level 1 500 AMG 531 (Part A - azacitidine)	Azacitidine	500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Dose level 1 500 AMG 531 (Part A - azacitidine)	AMG 531 (Romiplostim)	500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Placebo (Part B - decitabine)	Placebo	Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles
Dose level 1 750 AMG 531 (Part B - decitabine)	Decitabine	750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles
Dose level 2 750 AMG 531 (Part A - azacitidine)	Azacitidine	750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Placebo (Part A - azacitidine)	Azacitidine	Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles
Placebo (Part B - decitabine)	Decitabine	Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles

Primary Outcome Measures

Name	Time	Method
Occurrence of a Clinically Significant Thrombocytopenic Event	Treatment period (up to 20 weeks)	Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10\^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.

Secondary Outcome Measures

Name	Time	Method
Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period	Treatment period (up to 20 weeks)	CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10\^9/L, neutrophils ≥ 1x10\^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.
Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia	Treatment period (up to 20 weeks)	Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia
Platelet Transfusion	Study day 1 through the interim follow-up visit (up to 20 weeks)	Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)