High Risk Polycythemia Vera or High Risk Essential Thrombocythemia MedDRA version: 14.1 Level: PT Classification code 10036057 Term: Polycythaemia vera System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10015493 Term: Essential thrombocythaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Peginterferon PFS
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGINTERFERON ALFA-2A
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number:
Sponsors
CONSORZIO MARIO NEGRI SUD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: High risk PV ANY ONE of the following: Age >60 years Previous documented thrombosis, erythromelalgia or migraine either after diagnosis or within 10 years before diagnosis and considered to be disease related Significant (i.e. > 5cm below costal margin on palpation) or symptomatic (pain, early satiety) splenomegaly Platelets > 1000 x 109/L Diabetes or hypertension requiring pharmacological therapy High risk ET ANY ONE of the following factors: Age > 60 years Platelet count > 1500 x 109/L Previous thrombosis Previous hemorrhage related to ET Diabetes or hypertension requiring pharmacological therapy Other Inclusion criteria 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) Age: > 18 years (no upper limit) 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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 408 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 204
Exclusion criteria
Exclusion criteria: Exclusion criteria: (ANY of) 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 IFN-a HIV, HBV, or systemic infection Evidence of severe retinopathy (e.g. 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 Any investigational drug <6 weeks prior to the first dose of study drug Neutrophil count <1.5 x 109/L JAK2 exon 12 mutation Patients should not meet criteria for post PV or post ET-MF (see appendix B) No previous exposure to any formulation of pegylated interferon 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the complete hematologic response rates (by LeukemiaNet Criteria) in patients randomized to treatment with the Pegylated Interferon Alfa-2a (PEGASYS) vs. Hydroxyurea in two strata of patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia. All comparisons will be carried out separately within each disease stratum.;Secondary Objective: -toxicity, safety and tolerability of therapy. -hematologic partial response rates on therapy. -specific pre-defined toxicity and tolerance of therapy and validate the utility of sequential structured symptom assessment package of patient reported outcome instruments. -impact of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) to impact key biomarkers of the disease. -survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation. -incidence of major cardiovascular events.;Primary end point(s): Complete Response. Criteria for complete response in ET: -Platelet count 10 x 109/L AND -Normal spleen size on imaging AND -No disease related symptoms;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -To compare the toxicity, safety and tolerability of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) in the study populations. -To compare the hematologic partial response rates on therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) by LeukemiaNet criteria. -To compare specific pre-defined toxicity and tolerance of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) and validate the utility of sequential structured symptom assessment package of patient reported outcome instruments. -To compare the impact of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) to impact key biomarkers of the disease(s) – JAK2-V617F, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities. -To estimate survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea). -To estimate incidence of major cardiovascular events (defined as cardiovascular death, myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, Budd Chiari syndrome, deep vein thrombosis, and any other clinically relevant thrombotic event) after therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea).;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
Canada, Germany, Italy, Sweden, United Kingdom, United States
Contacts
Public ContactLaboratory of Clinical Epidemiology
CONSORZIO MARIO NEGRI SUD
Outcome results
None listed