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

Amgen

Status and phase: Completed; Phase 2

Conditions: MDS; Thrombocytopenia; Refractory Cytopenias; Myelodysplastic Syndromes

Treatments: Drug: Romiplostim

Study type: Interventional

Funder types: Industry

Identifiers

NCT00303472

20050159

Details and patient eligibility

About

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.

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 7 patient groups

Part A: 300 µg romiplostim

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part A: 700 µg romiplostim

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part A: 1000 µg romiplostim

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part A: 1500 µg romiplostim

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part B: 750 µg romiplostim SC QW

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part B: 750 µg romiplostim SC Q2W

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim

Part B: 750 µg romiplostim IV Q2W

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim