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

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.

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Thrombocytopenia
• Intervention / Treatment: Biological: AMG 531; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Wang ES, Lyons RM, Larson RA, Gandhi S, Liu D, Matei C, Scott B, Hu K, Yang AS. A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide. J Hematol Oncol. 2012 Nov 29;5:71. doi: 10.1186/1756-8722-5-71.

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: January 4, 2007
• First Submitted That Met QC Criteria: January 4, 2007
• First Posted (Estimate): January 5, 2007

Study Record Updates

• Last Update Posted (Estimate): January 24, 2011
• Last Update Submitted That Met QC Criteria: January 20, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Lenalidomide; MDS; Myelodysplastic Syndrome; Revlimid; Low Risk Myelodysplastic Syndrome; Low Platelet Count; Intermediate 1 Myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Blood Platelet Disorders; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Thrombocytopenia
• Other Study ID Numbers: 20060102 (BiPar)