Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia
Study Details
Study Description
Brief Summary
RATIONALE: Romiplostim may cause the body to make platelets.
PURPOSE: This randomized phase II trial is studying how well romiplostim works in treating hepatitis C-infected patients with thrombocytopenia.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To assess the platelet count response to administration of weekly romiplostim patients with HCV infection whose initial platelet count is < 70,000/L.
SECONDARY OBJECTIVES:
-
To assess the safety and tolerability of romiplostim the treatment of patients with HCV infection and thrombocytopenia; including physical symptoms and findings, hematologic, serum chemistries and liver function tests and adverse events.
-
To assess the ability of romiplostim to enable subjects to achieve a platelet count sufficient to start antiviral therapy.
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To assess the ability of romiplostim to maintain platelet counts greater than 50,000/L while receiving antiviral therapy with pegylated interferon and ribavirin.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive placebo subcutaneously once weekly for 8 weeks. Patients failing to achieve a platelet count of > 100,000/L cross over to arm I.
Patients achieving a platelet count of > 100,000/L at 8 weeks receive PEG-interferon alfa-2a subcutaneously once weekly and oral ribavirin once daily. Treatment repeats every 7 days for 24-48 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 4 and 36 weeks.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Arm I Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity. |
Biological: romiplostim
Given subcutaneously
Other Names:
Drug: ribavirin
Given orally
Other Names:
Biological: PEG-interferon alfa-2a
Given subcutaneously
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Placebo Comparator: Arm II Patients receive placebo subcutaneously once weekly for 8 weeks. Patients failing to achieve a platelet count of > 100,000/L cross over to arm I. |
Drug: ribavirin
Given orally
Other Names:
Other: placebo
Given subcutaneously
Other Names:
Biological: PEG-interferon alfa-2a
Given subcutaneously
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Mean platelet count for actively treated and placebo treated subjects [Weeks 6-8]
Secondary Outcome Measures
- Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation [Weeks 1-24]
- Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L [Week 8]
- Number of patients originally receiving active treatment who maintain a platelet count > 50,000/L while receiving anti-viral therapy with pegylated interferon and ribavirin [Weeks 9-24]
- Changes in plasma HCV viral load during treatment with romiplostim alone [Weeks 1-8]
- Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim [Weeks 9-24]
Eligibility Criteria
Criteria
Inclusion
-
All patients with HCV virus infection documented by detectable plasma HCV antibodies and RNA who would be excluded by FDA criteria for antiviral treatment with peginterferon-alpha 2a and ribavirin due to thrombocytopenia (platelets < 70,000/L); patients cannot have received previous anti-viral therapy with interferon/ribavirin
-
Liver biopsy indicating chronic hepatitis within the previous 2 years
-
Mean platelet count of < 70,000/L on two repeated measurements in a two week screening period with no single count >= 75,000/L
-
Neutrophil count of >= 1000/mcl
-
Hemoglobin >= 11gm/dL and no evidence of active bleeding
-
Prothrombin Time (PT) INR < 1.6 seconds
-
Albumin >= 2.5 gm/dL
-
ALT >= 1.2 and < 10 times upper limit of normal
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No evidence of either ischemic change or cardiac injury on 12-lead electrocardiogram (EKG)
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Negative pregnancy test and women must be using adequate contraception for at least 2 weeks prior to enrollment and while enrolled in the study
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Signed informed consent within 2 weeks of enrollment and randomization
Exclusion
-
Received previous anti-viral therapy with interferon/ribavirin
-
Child's Class B and C or acute decompensated liver disease
-
Human Immunodeficiency Virus (HIV) infection or co-infected with hepatitis B virus
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Any untreated active infection
-
Active malignancy, known primary bone marrow disorder (myelodysplasia, myeloproliferative disease, etc.), or history of blood or bone marrow transplantation; patients with documented hemoglobinopathies
-
Active vasculitis associated with cryoglobulinemia as manifested by either renal disease or dermatologic findings
-
Positive pregnancy test or men with pregnant partners
-
Creatinine and BUN of greater than twice (2x) the upper limits of normal
-
History of venous or arterial thrombosis, myocardial infarction or thrombotic stroke
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Patients who in the investigators opinion will fail to be compliant or have other contraindication to treatment on this study
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Other inherited or acquired liver disease
-
Previous solid organ transplant
-
Known hypersensitivity to E. coli derived recombinant proteins
-
Active rheumatologic disease including Systemic Lupus Erythematosis
-
Known history of Disseminated Intravascular Coagulation, Hemolytic Uremic Syndrome, or Thrombotic Thrombocytopenic Purpura
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | USC/Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
Sponsors and Collaborators
- University of Southern California
Investigators
- Principal Investigator: Howard Liebman, University of Southern California
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NC-HEM-07-5
- NCI-2010-00358