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

Overview

The trial will be a phase III, randomised-controlled, multi-centre, international, open-label trial consisting of ruxolitinib versus best available therapy, where best available therapy is a choice of interferon alpha, any formulation permitted (IFN) or hydroxycarbamide (HC), and which will be elected by the Investigator prior to randomisation.

Description

The trial will be a phase III, randomised-controlled, multi-centre, international, open-label trial consisting of ruxolitinib versus best available therapy, where best available therapy is a choice of interferon alpha, any formulation permitted (IFN) or hydroxycarbamide (HC), and which will be elected by the Investigator prior to randomisation.

There will be no cross-over either between arm A and B or between therapies on Arm B

HC and IFN will be provided as best available therapy, IFN can include standard of pegylated-interferon at Investigators discretion.

Eligibility

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 (At any time since diagnosis)

Inclusion Criteria:

1. Patient ≥18 years of age
2. Diagnosis of PV meeting the WHO criteria within the past 10 years
3. Meets criteria of high risk* PV (see above for specific population)
4. Patients may have received antiplatelet agents and venesection
5. Patients may have received ONE cytoreductive therapy for PV less than 5 years (BUT they should not be resistant or intolerant to that therapy)
6. Able to provide written informed consent

Exclusion Criteria:

1. Diagnosis of PV > 10 years previously
2. Absence of any JAK-2 mutation
3. Patients with any contraindications to any of the investigational medical products
4. Treatment with >1 cytoreductive therapy OR a cytoreductive treatment duration exceeding 5 years OR resistance/intolerance to that therapy
5. Active infection including hepatitis B, hepatitis C, Tuberculosis
6. Pregnant or lactating patients (Women of childbearing potential must have a negative urine or blood Human Chorionic Gonadotropin pregnancy test prior to trial entry)
7. Patients and partners of childbearing potential 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
8. ECOG Performance Status Score ≥ 3
9. Uncontrolled rapid or paroxysmal atrial fibrillation, uncontrolled or unstable angina, recent (6 months) myocardial infarction or acute coronary syndrome or any clinically significant cardiac disease > NYHA (New York Heart Association) Class II
10. Patients who have transformed to myelofibrosis
11. Previous treatment with ruxolitinib
12. 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
13. Inadequate liver function as defined by ALT/AST > 2.0 x ULN
14. Inadequate renal function as defined by eGFR < 30 ml/min
15. Unable to give informed consent