PEG-Interferon Alfa-2a or Hydroxyurea in Treating Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia

Inclusion Criteria

• A diagnosis of ET or PV shall be made in accordance with the World Health Organization (WHO) (2008) criteria (Swerdlow 2008)
• Diagnosis < 3 years prior to entry
• Polycythemia Vera (2 major criteria required) * Hemoglobin (Hb) > 18.5g/dl (male) or 16.5g/dl (female) or * Hematocrit (HCT) > 99 percentile reference range or * Elevated red cell mass (> 25% above mean predicted value) or * Hb > 17g/dl (male) or 15g/dl (female) if associated with a sustained rise from baseline with no apparent cause (e.g. treated iron deficiency) * Presence of JAK2V617F
• Essential Thrombocythemia (all 4 major criteria required) * Platelets count >= 450 x 10^9/L * Megakaryocyte proliferation with large and mature morphology; no significant increase or left shift of neutrophil granulopoiesis or erythropoiesis * Not meeting WHO criteria for chronic myelogenous leukemia (CML), PV, myelodysplastic syndromes (MDS) or other myeloid neoplasms * Demonstration of clonal cytogenetic marker or no evidence of reactive thrombocytosis * May participate in study without presence of JAK2V617F
• Patients must have high risk disease as defined below: * High risk PV ANY ONE of the following: ** Age >= 60 years ** Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the myeloproliferative neoplasm [MPN]) either after diagnosis or within 10 years before diagnosis and considered to be disease related ** Significant splenomegaly (> 5 cm below the left costal margin) or symptomatic splenomegaly (splenic infarcts or requiring analgesia) ** Platelets > 1000 x 10^9/L ** Diabetes or hypertension requiring pharmacological therapy for > 6 months * High risk ET ANY ONE of the following: ** Age >= 60 years ** Platelet count > 1500 x 10^9/L ** Previous documented thrombosis, erythromelalgia or migraine headaches (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related ** Previous hemorrhage related to ET ** Diabetes or hypertension requiring pharmacological therapy for > 6 months
• Diagnosed less than 3 years prior to entry on trial
• Never treated with cytoreductive drugs except hydroxyurea for up to 3 months maximum (phlebotomy, aspirin allowed, anagrelide allowed)
• Ability and willingness to comply with all study requirements
• Signed informed consent to participate in this study
• Willing to participate in associated correlative science biomarker study
• Serum creatinine =< 1.5 x upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit of normal
• Total bilirubin within normal limits
• No known PNH (paroxysmal nocturnal hemoglobinuria) clone
• No concurrent hormonal oral contraceptive use

Exclusion Criteria

• Any contraindications to pegylated interferon or hydroxyurea
• Presence of any life-threatening co-morbidity
• History of active substance or alcohol abuse within the last year
• Subjects who are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception
• History of psychiatric disorder (e.g. depression)
• History of autoimmune disorder (e.g. hepatitis)
• Hypersensitivity to interferon alfa
• Hepatitis B or C infection (HBV), or untreated systemic infection
• Known human immunodeficiency virus (HIV) disease
• Evidence of severe retinopathy (e.g. cytomegalovirus [CMV] retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension)
• History or other evidence of decompensated liver disease
• Splanchnic vein thrombosis (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
• History or other evidence of chronic pulmonary disease associated with functional limitation
• Thyroid dysfunction not adequately controlled
• Neutrophil count < 1.5 x 10^9/L
• JAK2 exon 12 mutation: PV that lacks the JAK2V617F mutation but is characterized by the exon 12 mutation
• Patients should not meet criteria for post PV or post ET-myelofibrosis (MF)
• Subjects with any other medical condition, which in the opinion of the investigator would compromise the results of the study by deleterious effects of treatment
• No previous exposure to any formulation of pegylated interferon
• History of major organ transplantation
• History of uncontrolled severe seizure disorder
• Inability to give informed written consent
• Serum creatinine >= 1.5 x upper limit of normal
• AST and ALT >= 2 x upper limit of normal