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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321711
• Other study ID #: 20050232
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2006
• Est. completion date: October 19, 2009

Study information

• Verified date: September 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: October 19, 2009
• Est. primary completion date: October 19, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• MDS
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome
• Thrombocytopenia

Intervention

Drug:
• Placebo
Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.

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
• Decitabine
hypomethylating agent

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

Greenberg PL, Garcia-Manero G, Moore M, Damon L, Roboz G, Hu K, Yang AS, Franklin J. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine. Leuk Lymphoma. 2013 Feb;54(2):321-8. doi: 10.3109/10428194.2012.713477. Epub 2012 Nov 15. — View Citation

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. doi: 10.1182/blood-2010-03-274753. Epub 2010 Jul 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of a Clinically Significant Thrombocytopenic Event	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.	Treatment period (up to 20 weeks)
Secondary	Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia	Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia	Treatment period (up to 20 weeks)
Secondary	Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period	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 (up to 20 weeks)
Secondary	Platelet Transfusion	Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)	Study day 1 through the interim follow-up visit (up to 20 weeks)

External Links

•   AmgenTrials clinical trials website