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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of AMG 531 Treatment of Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) Receiving Lenalidomide.

Conditions
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Myelodysplastic Syndromes, Thrombocytopenia

Intervention / Treatment
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* Biological: AMG 531
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 750 mcg AMG 531<br>750 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A) | Biological: AMG 531<br>* AMG 531 will be administered by subcutaneous injection at a dose of 500 or 750 μg.<br>|
| Placebo Comparator: Placebo Part B<br>Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B) | Drug: Placebo<br>* Subjects in the control group will receive placebo via subcutaneous injection.<br>|
| Placebo Comparator: Placebo Part A<br>Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A) | Drug: Placebo<br>* Subjects in the control group will receive placebo via subcutaneous injection.<br>|
| Active Comparator: 500 mcg AMG 531<br>500 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A) | Biological: AMG 531<br>* AMG 531 will be administered by subcutaneous injection at a dose of 500 or 750 μg.<br>|
| Active Comparator: 750 mcg AMG531 Part B<br>750 μg AMG 531 biweekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B) | Biological: AMG 531<br>* AMG 531 will be administered by subcutaneous injection at a dose of 500 or 750 μg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of a Clinically Significant Thrombocytopenic Event | 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. | Treatment period through interim follow-up visit (up to 16 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lenalidomide Dose Reduction and Delay Due to Thrombocytopenia | Occurrence of lenalidomide dose reduction and delay due to thrombocytopenia | Treatment period (up to 16 weeks) | 
| 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 | 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. | Treatment period and post-treatment follow-up (up to 21 weeks) | 
| Platelet Transfusion | Occurrence of one or more platelet transfusions during the treatment period | Treatment period (up to 16 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Revlimid, Lenalidomide, Low Platelet Count, Low Risk Myelodysplastic Syndrome, Intermediate 1 Myelodysplastic Syndrome, MDS, Myelodysplastic Syndrome