Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)

NCT00303472 | Completed Phase 2 Results

• 1 other identifier: 20050159
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim.

Conditions

Thrombocytopenia; MDS; Myelodysplastic Syndromes; Refractory Cytopenias

Keywords

MDS; Myelodysplastic Syndromes; Refractory Cytopenias; Thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• Part A: Number of Participants With Adverse Events

  The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.

  Treatment period (4 weeks) plus treatment extension (1 year)

• Part B: Number of Participants With Adverse Events

  The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.

  Treatment period (8 weeks) plus treatment extension (1 year)

Secondary Outcomes (15)

• Part A: Number of Participants With a Complete or Major Platelet Response

  Treatment Period (4 weeks)

• Part B: Number of Participants With a Complete or Major Platelet Response

  Treatment Period (8 weeks)

• Part A: Number of Participants With a Platelet Response Per IWG Criteria

  Treatment period (4 weeks) and extension period (52 weeks).

• Part B: Number of Participants With a Platelet Response Per IWG

  Treatment period (8 weeks) and extension period (52 weeks).

• Part B: Peak Platelet Count

  Treatment Period (8 weeks)

Study Arms (7)

Part A: 300 µg romiplostim

EXPERIMENTAL

Cohort 1 in Part A, participants received romiplostim 300 µg subcutaneously once weekly for 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part A: 700 µg romiplostim

EXPERIMENTAL

Cohort 2 in Part A, participants received romiplostim 700 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part A: 1000 µg romiplostim

EXPERIMENTAL

Cohort 3 in Part A, participants received romiplostim 1000 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part A: 1500 µg romiplostim

EXPERIMENTAL

Cohort 4 in Part A, participants received romiplostim 1500 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part B: 750 µg romiplostim SC QW

EXPERIMENTAL

Part B participants received romiplostim 750 µg subcutaneously (SC) once weekly (QW) for 8 weeks. Participants who complete Part B could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part B: 750 µg romiplostim SC Q2W

EXPERIMENTAL

Part B participants received romiplostim 750 µg subcutaneously every two weeks (Q2W) for 8 weeks. Participants who complete Part B could continue to receive injections of romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Part B: 750 µg romiplostim IV Q2W

EXPERIMENTAL

Part B participants received romiplostim 750 µg intravenously (IV) once every two weeks for 8 weeks. Participants who complete Part B could continue to receive romiplostim for up to 1 year in the extension treatment phase.

Drug: Romiplostim

Interventions

Romiplostim DRUG

Also known as: AMG 531, Nplate®

Part A: 1000 µg romiplostim; Part A: 1500 µg romiplostim; Part A: 300 µg romiplostim; Part A: 700 µg romiplostim; Part B: 750 µg romiplostim IV Q2W; Part B: 750 µg romiplostim SC Q2W; Part B: 750 µg romiplostim SC QW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MDS using the World Health Organization classification
• Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS)
• The mean of two platelet counts taken during the screening period must be ≤ 50 x 10\^9/L, with no individual count \> 55 x 10\^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be ≤ 20 x 10\^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1.
• Must be ≥ 18 years of age at the time of obtaining informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
• Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate aminotransferase (AST) ≤ 3 times the laboratory normal range
• A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L)
• Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)

You may not qualify if:

• Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1
• Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage)
• Prior malignancy (other than controlled prostate cancer, 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 screening
• Prior history of bone marrow transplantation
• Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count \> 1,000/µL)
• Unstable angina, congestive heart failure (New York Heart Association \[NYHA\] \> class II), uncontrolled hypertension (diastolic \> 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
• Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
• Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening
• Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening
• Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor \[G-CSF; Neupogen, Granocyte\], pegfilgrastim \[Neulasta\], granulocyte macrophage-colony stimulating factor \[GM-CSF; Leukine, Prokine, Sargramostim\])
• Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim
• Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication
• Other investigational procedures are excluded
• History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year
• History of venous thrombosis that currently requires anti-coagulation therapy

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Kantarjian H, Fenaux P, Sekeres MA, Becker PS, Boruchov A, Bowen D, Hellstrom-Lindberg E, Larson RA, Lyons RM, Muus P, Shammo J, Siegel R, Hu K, Franklin J, Berger DP. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol. 2010 Jan 20;28(3):437-44. doi: 10.1200/JCO.2009.24.7999. Epub 2009 Dec 14.

  PMID: 20008626 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Thrombocytopenia; Myelodysplastic Syndromes; Cytopenia

Interventions

romiplostim

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2006
• First Posted: March 17, 2006
• Study Start: February 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: December 16, 2013
• Results First Posted: November 19, 2010

Record last verified: 2013-11