Ruxolitinib versus hydroxycarbamide or interferon as first-line therapy in high-risk polcythemia vera
Polycythemia Vera / Posted 11 months ago
Brief Summary:
A phase III, randomised, open-label, Multicenter International Trial comparing ruxolitinib with either HydRoxycarbamIDe or interferon Alpha as first-line ThErapy for high-risk polycythemia vera (MITHRIDATE)
Detailed Summary:
The interventions are Arm A: Ruxolitinib and Arm B: Best Available Therapy (Hydroxycarbamide OR Interferon Alpha, any formulation permitted), which will be selected by the Investigator prior to randomisation. Randomisation will be in a 1:1 ratio and will be performed using a bespoke computer randomisation system developed by the Cancer Research UK Clinical Trials Unit (CRCTU) employing a stratified minimisation method.
Patients will be stratified by:
1. Country of Origin: UK, France
2. Elected standard of care therapy: IFN, HC
3. Age: <60, ≥ 60
4. Prior thrombosis: No, Yes
5. Length of time from diagnosis: <5: ≥5 years
6. Cardiovascular risk factors, (including the following: arterial hypertension, diabetes, dyslipidemia, tobacco use, obesity): No, Yes
Randomisation will be in a 1:1 ratio AND There will be no cross-over either between arm A and B or between therapies on Arm B.
Arm A: Ruxolitinib – starting dose of 10 mg adjusted in line with the summary product of characteristics throughout for treatment period of 3 years
Arm B: Best Available Therapy (Hydroxycarbamide OR interferon alpha (any formulation permitted)) – treatment for 3 years, dosage is in line with the summary product of characteristics
Patients will be required to attend for study visits to monitor their disease, as they would do whilst following standard care. In addition, patients will be asked to consent to complete quality of life questionnaires every few months and have an additional bone marrow biopsy and an ultrasound scan at 3 years.
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Inclusion Criteria :
- 1. Patient 18 years of age or over
- 2. Diagnosis of PV meeting WHO criteria within past 10 years
- 3. Meets criteria of high risk* PV, defined as WBC > 11 x 109/l* AND at least ONE of the following:
- 3.1. Age > 60 years
- 3.2. Prior thrombosis or major haemorrhage related to disease
- 3.3. Platelet count > 1000 x 109/l*
- 3.4. Diagnosed < 10 years
- 3.5. Received treatment for < 5 years)
- 4. Patients may have received antiplatelet agents and venesection
- 5. Patients may have received ONE or less cytoreductive therapy for less than 5 years (BUT they should not be resistant or intolerant to that therapy)
- 6. Able to provide written informed consent
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Exclusion Criteria :
- 1. Diagnosis of PV > 10 years previously
- 2. Absence of 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 (within the last 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 mls/min
- 15. Unable to give informed consent
- Study end date : September 2029
- Wales-Based Study Contact : Please speak to your clinician
- Principal Investigator : Prof Claire Harrison (Guy's and St Thomas' NHS Foundation Trust)