A Safety and Efficacy Study to Evaluate AMG 531 Treatment in Subject With Myelodysplastic Syndrome Receiving Revlimid

Phase 2

Completed

Brief Summary: This is a dose and schedule finding study of AMG 531 designed to assess the activity of AMG 531 to reduce the rate of clinically significant bleeding and blood transfusions in subjects with myelodysplastic syndrome (MDS) receiving lenalidomide. Subjects with MDS that are planned to receive at least four cycles of lenalidomide for treatment of their disease are appropriate to screen for this study.

All subjects meeting the eligibility criteria will receive lenalidomide 10 mg capsule by mouth daily every day of each 28-day cycle. Subjects will receive AMG 531 or placebo once a week by subcutaneous injection for 16 weeks.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification
Low or Intermediate-1 risk category MDS using the IPSS
Planned to receive lenalidomide 10 mg capsule by mouth daily for all 28 days of each cycle for at least 4 cycles
Eastern Cooperative Oncology (ECOG) performance status of 0-2
Subjects must be at least 18 years of age or older

Exclusion Criteria

Prior exposure to >3 cycles of lenalidomide
Exposure to lenalidomide within the last 30 days
Prior history of leukemia or aplastic anemia
Prior history of stem cell 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 years before randomization
Active or uncontrolled infections
Unstable angina, congestive heart failure [NYHA > 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 in the past year
Received IL-11 within 4 weeks of screening
Less than 4 weeks since receipt of any investigational drug or device
Have previously received any other thrombopoietic growth factor
Pregnant or breast feeding
Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
Known hypersensitivity to any recombinant E coli-derived product

Arm && Interventions

Group	Intervention	Description
Placebo Part A	Placebo	Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)
500 mcg AMG 531	AMG 531	500 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)
750 mcg AMG531 Part B	AMG 531	750 μg AMG 531 biweekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B)
750 mcg AMG 531	AMG 531	750 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)
Placebo Part B	Placebo	Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B)

Primary Outcome Measures

Name	Time	Method
Occurrence of a Clinically Significant Thrombocytopenic Event	Treatment period through interim follow-up visit (up to 16 weeks)	Occurrence of one or more clinically significant thrombocytopenic events, defined as either Common Terminology Criteria for Adverse Events (CTCAE) v. 3 grade 3 or 4 thrombocytopenia starting from week 3 of cycle 1 or receipt of platelet transfusions starting from week 1 of cycle 1 and continuing through the end of treatment visit.

Secondary Outcome Measures

Name	Time	Method
Lenalidomide Dose Reduction and Delay Due to Thrombocytopenia	Treatment period (up to 16 weeks)	Occurrence of lenalidomide dose reduction and delay due to thrombocytopenia
Achieving an Overall Response (Complete Response (CR) or Partial Response (PR)) Determined by the Investigator Based on Modified International Working Group 2006 Response Criteria Guidelines	Treatment period and post-treatment follow-up (up to 21 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.
Platelet Transfusion	Treatment period (up to 16 weeks)	Occurrence of one or more platelet transfusions during the treatment period