MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polycythemia Vera

Prior treatment

• Diagnosis of PV \> 15 years previously
• Treatment with \>1 cytoreductive therapy OR a cytoreductive treatment duration exceeding 10 years OR resistance/intolerance to that therapy
• Pregnant or lactating patients (Women of childbearing potential must have a negative urine or blood Human Chorionic Gonadotropin pregnancy test prior to trial entry)
• Patients and partners not prepared to adopt highly effective contraception measures (if sexually active) whilst on treatment and for at least 6 months after completion of study medication
• Previous treatment with ruxolitinib

Other illness

• Active infection including Human Immunodeficiency Virus (HIV), hepatitis B, hepatitis C, autoimmune hepatitis, Tuberculosis
• Patients with uncontrolled neuropsychiatric disorders
• Patients with uncontrolled cutaneous cancers
• Uncontrolled rapid or paroxysmal atrial fibrillation, uncontrolled or unstable angina, recent (within the last 6 months) myocardial infarction or acute coronary syndrome or any clinically significant cardiac disease \> NYHA ( New York Heart Association) Class II
• Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up

Lab values

• Patients with lactose allergies, hypersensitivities, or rare hereditary problems, of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption
• Previous (within the last 12 months) or current platelet count \<100 x 109/L or neutrophil count \< 1 x 109/L not due to therapy
• Inadequate liver function as defined by ALT/AST \>2.0 x ULN
• Inadequate renal function as defined by eGFR \< 30 mls/min

Other

• Absence of JAK-2 mutation
• Patients with any contraindications to any of the investigational medical products
• ECOG Performance Status Score ≥ 3
• Patients who have transformed to myelofibrosis
• Unable to give informed consent
  • Additional Exclusion Criteria for France Only
• All women of childbearing potential (as per Appendix 8 definition)
• No affiliation with the French healthcare system
• Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
• Patients deprived of their liberty by a judicial or administrative decision

• Patient ≥18 years of age
• Diagnosis of PV meeting the WHO criteria within the past 15 years
• Meets criteria of high risk\* PV (see above for specific population)
• Patients must have a screening haemoglobin of \>8g/dl
• Patients may have received antiplatelet agents and venesection
• Patients may have received ONE cytoreductive therapy for PV less than 10 years (BUT they should not be resistant or intolerant to that therapy)
• Able to provide written informed consent

Criteria the registry did not label

• Population:
• High risk PV defined as WBC \>11 x 10\^9/l\* AND at least ONE of the following
• Age \>60 years
• Prior thrombosis or haemorrhage
• Platelet count \>1000 x 10\^9/l\*
• Hypertension or diabetes requiring pharmacological therapy (\*At any time since diagnosis)