Determination of Safe and Effective Dose of AMG 531 in Subjects With MDS Receiving Hypomethylating Agents - Full Text View

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

Purpose

The purpose of this study is to evaluate the effect of 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 MDS receiving hypomethylating agents. It is hypothesized that AMG 531 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	Phase II

Drug Information available for: AMG 531

U.S. FDA Resources

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

Further study details as provided by Amgen:

Primary Outcome Measures:

The overall incidence of clinically significant thrombocytopenic events during the treatment period. [ Time Frame: During the treatment period (Cycle 1-4) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The overall incidence and severity of all adverse events. [ Time Frame: For the duration of the study ] [ Designated as safety issue: Yes ]
The overall incidence of hypomethylating agent dose reduction and delay due to thrombocytopenia. [ Time Frame: During the treatment period (Cycle 1-4) ] [ Designated as safety issue: No ]
The proportion of subejcts achieving an overal response (CR+PR), complete response (CR) or partial respone (PR) at the end of the treatment period. [ Time Frame: During the treatment period (Cycle 1-4) ] [ Designated as safety issue: No ]
The incidence of platelet transfusions [ Time Frame: For the duration of the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	108
Study Start Date:	October 2006
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Dose Level 2 AMG 531 (Part B - decitabine): Active Comparator Following DRT review of Part A, dose level in Part B will be confirmed. Dose level 2 AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles	Biological: AMG 531 AMG 531 will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during the 4 cycle treatment period, depending on randomization.
Dose Level 1 AMG 531 (Part B - decitabine): Active Comparator Following DRT review of Part A, dose level in Part B will be confirmed. Dose level 1 AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles	Biological: AMG 531 AMG 531 will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during the 4 cycle treatment period, depending on randomization.
AMG 531 500 mcg (Part A - azacitidine): Active Comparator 500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles	Biological: AMG 531 AMG 531 will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during the 4 cycle treatment period, depending on randomization.
AMG 531 750 mcg (Part A - azacitidine): Active Comparator 750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles	Biological: AMG 531 AMG 531 will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during the 4 cycle treatment period, depending on randomization.
Placebo (Part A - azacitidine): Placebo Comparator 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.
Placebo (Part B - decitabine): Placebo Comparator 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.

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 - 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 > 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

Contacts

Contact: Amgen Call Center

866-572-6436

Show 63 Study Locations

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

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

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20050232
Study First Received:	May 2, 2006
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00321711
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amgen:

MDS
Myelodysplastic Syndromes
Refractory Cytopenias
Thrombocytopenia

Study placed in the following topic categories:

Myelodysplastic syndromes
Thrombocytopathy
Preleukemia
Thrombocytopenia
Precancerous Conditions

Hematologic Diseases
Blood Platelet Disorders
Myelodysplasia
Myelodysplastic Syndromes
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease
Syndrome

ClinicalTrials.gov processed this record on January 16, 2009