Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00303472
First received: March 16, 2006
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Thrombocytopenia
MDS
Myelodysplastic Syndromes
Refractory Cytopenias
Drug: Romiplostim
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Part A: Number of Participants With Adverse Events [ Time Frame: Treatment period (4 weeks) plus treatment extension (1 year) ] [ Designated as safety issue: Yes ]
    The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.

  • Part B: Number of Participants With Adverse Events [ Time Frame: Treatment period (8 weeks) plus treatment extension (1 year) ] [ Designated as safety issue: Yes ]
    The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.


Secondary Outcome Measures:
  • Part A: Number of Participants With a Complete or Major Platelet Response [ Time Frame: Treatment Period (4 weeks) ] [ Designated as safety issue: No ]
    Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets, or an increase from ≤ 20 x 10^9/L to > 20 x 10^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.

  • Part B: Number of Participants With a Complete or Major Platelet Response [ Time Frame: Treatment Period (8 weeks) ] [ Designated as safety issue: No ]
    Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets, or an increase from ≤ 20 x 10^9/L to > 20 x 10^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.

  • Part A: Number of Participants With a Platelet Response Per IWG Criteria [ Time Frame: Treatment period (4 weeks) and extension period (52 weeks). ] [ Designated as safety issue: No ]
    The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10^9/L with Baseline platelet count > 20 x 10^9/L, or with a Baseline count ≤ 20 x 10^9/L, increasing to above 20 x 10^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.

  • Part B: Number of Participants With a Platelet Response Per IWG [ Time Frame: Treatment period (8 weeks) and extension period (52 weeks). ] [ Designated as safety issue: No ]
    The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10^9/L with Baseline platelet count > 20 x 10^9/L, or with a Baseline count ≤ 20 x 10^9/L, increasing to above 20 x 10^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.

  • Part B: Peak Platelet Count [ Time Frame: Treatment Period (8 weeks) ] [ Designated as safety issue: No ]
    Peak platelet count (10^9/L) during the treatment period.

  • Part B: Time to First Platelet Response [ Time Frame: Treatment Period (8 weeks) and extension period (52 weeks). ] [ Designated as safety issue: No ]
    Participants achieving first platelet response according to IWG criteria, by study week. Platelet response was defined as an absolute increase of ≥ 30 x 10^9/L with Baseline platelet count > 20 x 10^9/L, or with a Baseline ≤ 20 x 10^9/L increasing the platelet count to above 20 x 10^9/L and by at least 100% for 8 consecutive weeks. Platelet counts obtained within 72 hours of platelet transfusion were not evaluable for platelet response.

  • Part B: Duration of Platelet Response [ Time Frame: Treatment Period (8 weeks) and extension period (52 weeks) ] [ Designated as safety issue: No ]
    Duration of platelet response per IWG criteria (absolute increase of ≥ 30 x 10^9/L with Baseline platelet count > 20 x 10^9/L, or with a Baseline ≤ 20 x 10^9/L increasing the platelet count to above 20 x 10^9/L and by at least 100% for 8 consecutive weeks).

  • Part B: Week 1 Cmax [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    Maximum observed serum concentration (Cmax) of romiplostim during Week 1

  • Part B: Week 1 Ctrough [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    Measured romiplostim concentration at the end of the week 1 dosing interval (Ctrough)

  • Part B: Week 1 AUC0-4 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 1

  • Part B: Week 7 Cmax [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    Maximum observed serum concentration (Cmax) of romiplostim during Week 7.

  • Part B: Week 7 Ctrough [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    Measured romiplostim concentration at the end of the Week 7 dosing interval (Ctrough)

  • Part B: Week 7 AUC0-4 [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 7.

  • Part B: Week 1 Tmax [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 1

  • Part B: Week 7 Tmax [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 7


Enrollment: 72
Study Start Date: February 2006
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: 300 µg romiplostim
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part A: 700 µg romiplostim
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part A: 1000 µg romiplostim
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part A: 1500 µg romiplostim
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part B: 750 µg romiplostim SC QW
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part B: 750 µg romiplostim SC Q2W
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
Other Names:
  • AMG 531
  • Nplate®
Experimental: Part B: 750 µg romiplostim IV Q2W
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
Other Names:
  • AMG 531
  • Nplate®

  Eligibility

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

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • Untreated B12 or folate deficiency
  • Subject is evidently pregnant (eg, positive human chorionic gonadotropin [HCG] test) or is breast feeding
  • Subject is not using adequate contraceptive precautions
  • Subject has known hypersensitivity to any recombinant E coli-derived product
  • Subject previously has enrolled in this study
  • Subject will not be available for follow-up assessment
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303472

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00303472     History of Changes
Obsolete Identifiers: NCT00548028
Other Study ID Numbers: 20050159
Study First Received: March 16, 2006
Results First Received: October 22, 2010
Last Updated: November 21, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Sweden: Medical Products Agency
United States: Food and Drug Administration

Keywords provided by Amgen:
MDS
Myelodysplastic Syndromes
Refractory Cytopenias
Thrombocytopenia

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Thrombocytopenia
Blood Platelet Disorders
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on November 23, 2014