Polycythaemia vera Cancer Polycythaemia vera
Conditions
Interventions
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 random
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 06/06/2025: 1. Patient = 18 years of age 2. Diagnosis of PV meeting WHO criteria within the past 15 years 3. Meets criteria of high-risk PV, defined as WBC >11 x 10(9)/l* AND at least ONE of the following: 3.1. Aged >60 years 3.2. Prior thrombosis or major haemorrhage related to disease 3.3. Platelet count >1000 x 10(9)/l* 3.4. Hypertension or diabetes requiring pharmacological therapy * at any time after diagnosis 4. Patients must have a screening haemoglobin of >8g/dl 5. Patients may have received antiplatelet agents and venesection 6. Patients may have received ONE or less cytoreductive therapy for less than 10 years (BUT they should not be resistant or intolerant to that therapy) 7. Able to provide written informed consent _____ Previous participant inclusion criteria as of 09/05/2023: 1. Patient 18 years of age or over 2. Diagnosis of PV meeting WHO criteria within the past 10 years 3. Meets criteria of high-risk PV, defined as WBC >11 x 10(9)/l AND at least ONE of the following: 3.1. Aged >60 years 3.2. Prior thrombosis or major haemorrhage related to disease 3.3. Platelet count >1000 x 10(9)/l at any time after diagnosis 3.4. Diagnosed 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
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 06/06/2025: 1. Diagnosis of PV > 15 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 10 years OR resistance/intolerance to that therapy 5. Active infection including Human Immunodeficiency Virus (HIV), hepatitis B, hepatitis C, autoimmune hepatitis, 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 with lactose allergies, hypersensitivities, or rare hereditary problems, of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 8. Patients with uncontrolled neuropsychiatric disorders 9. Patients with uncontrolled cutaneous cancers 10. 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 11. ECOG Performance Status Score = 3 12. 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 13. Patients who have transformed to myelofibrosis 14. Previous treatment with ruxolitinib 15. Previous (within the last 12 months) or current platelet count 2.0 x ULN 17. Inadequate renal function as defined by eGFR 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 las
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event Free Survival (EFS): defined as the time from randomisation to the date of the first event including; 1. Major thrombosis 2. Major haemorrhage 3. Death 4. Transformation to MDS, AML or PPV-MF Patients who do not experience an event during the trial will be censored at their date last seen | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Major thrombosis (both combined and split into venous and arterial) 2. Major haemorrhage 3. Transformation to PPV-MF 4. Transformation to AML and/or MDS 5. Complete haematological response (CHR) as defined by ELN response criteria at 1 year 6. Symptom burden/(QALY) quality of life years gained 7. Health economics including cost-utility and cost-effectiveness analyses 8. Peripheral blood JAK2 V617F allele burden according to ELN response criteria 9. Rates of discontinuation 10. Adverse events 11. Spleen response in patients with splenomegaly at baseline 12. Time free from venesection 13. Rate of second malignancies 14. Change in QRisk score | — |
Countries
England, France, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed