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

Sponsor:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00321711

Purpose

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.

Condition	Intervention	Phase
MDS Myelodysplastic Syndromes Thrombocytopenia	Drug: Placebo Biological: AMG 531 (Romiplostim) Drug: Azacitidine Drug: Decitabine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Supportive Care
Official Title:	A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim (AMG 531) Treatment of Subjects With Low or Intermediate Risk Myelodysplastic Syndrome (MDS) Receiving Hypomethylating Agents

Resource links provided by NLM:

Genetics Home Reference related topics: MYH9-related disorder

MedlinePlus related topics: Myelodysplastic Syndromes

Drug Information available for: AMG 531 Azacitidine 5-Aza-2'-deoxycytidine

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Occurrence of a Clinically Significant Thrombocytopenic Event [ Time Frame: Treatment period (up to 20 weeks) ] [ Designated as safety issue: No ]
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:

Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia [ Time Frame: Treatment period (up to 20 weeks) ] [ Designated as safety issue: No ]
Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia
Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period [ Time Frame: Treatment period (up to 20 weeks) ] [ Designated as safety issue: No ]
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 [ Time Frame: Study day 1 through the interim follow-up visit (up to 20 weeks) ] [ Designated as safety issue: No ]
Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)

Enrollment:	69
Study Start Date:	October 2006
Study Completion Date:	October 2010
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Dose level 1 500 AMG 531 (Part A - azacitidine) 500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles	Biological: AMG 531 (Romiplostim) AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization. Drug: Azacitidine hypomethylating agent
Active Comparator: Dose level 1 750 AMG 531 (Part B - decitabine) 750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles	Biological: AMG 531 (Romiplostim) AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization. Drug: Decitabine hypomethylating agent
Active Comparator: Dose level 2 750 AMG 531 (Part A - azacitidine) 750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles	Biological: AMG 531 (Romiplostim) AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization. Drug: Azacitidine hypomethylating agent
Placebo Comparator: Placebo (Part A - azacitidine) Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles	Drug: Placebo Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period. Drug: Azacitidine hypomethylating agent
Placebo Comparator: Placebo (Part B - decitabine) Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles	Drug: Placebo Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period. Drug: Decitabine hypomethylating agent

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00321711

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

Notice regarding posted summaries of trial results This link exits the ClinicalTrials.gov site

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010 Oct 28;116(17):3163-70. Epub 2010 Jul 14.

Responsible Party:	Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier:	NCT00321711 History of Changes
Other Study ID Numbers:	20050232
Study First Received:	May 2, 2006
Results First Received:	November 18, 2010
Last Updated:	June 3, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amgen:

MDS
Myelodysplastic Syndromes
Refractory Cytopenias
Thrombocytopenia

Additional relevant MeSH terms:

Myelodysplastic Syndromes
Preleukemia
Thrombocytopenia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Blood Platelet Disorders
Azacitidine

Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012