MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polycythemia Vera
- Conditions
- Polycythemia Vera
- Interventions
- Registration Number
- NCT04116502
- Lead Sponsor
- University of Birmingham
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 586
- 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
-
Diagnosis of PV > 15 years previously
-
Absence of JAK-2 mutation
-
Patients with any contraindications to any of the investigational medical products
-
Treatment with >1 cytoreductive therapy OR a cytoreductive treatment duration exceeding 10 years OR resistance/intolerance to that therapy
-
Active infection including Human Immunodeficiency Virus (HIV), hepatitis B, hepatitis C, autoimmune hepatitis, Tuberculosis
-
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 with lactose allergies, hypersensitivities, or rare hereditary problems, of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption
-
Patients with uncontrolled neuropsychiatric disorders
-
Patients with uncontrolled cutaneous cancers
-
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
-
ECOG Performance Status Score ≥ 3
-
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
-
Patients who have transformed to myelofibrosis
-
Previous treatment with ruxolitinib
-
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
-
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
-
Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up
-
Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
-
Patients deprived of their liberty by a judicial or administrative decision
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B- Hydroxycarbamide OR Interferon A Interferon-Alpha Best Available Therapy (BAT), Treatment with hydroxycarbamide OR Interferon A A- Ruxolitinib Ruxolitinib Treatment with Ruxolitinib B- Hydroxycarbamide OR Interferon A Hydroxycarbamide Best Available Therapy (BAT), Treatment with hydroxycarbamide OR Interferon A
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) the time from randomisation to the date of the first major thrombosis/haemorrhage, death,transformation to Myelodysplastic Syndromes, Acute Myeloid Leukaemia or Post-polycythemia Vera Myelofibrosis, if within the ~3 year trial period Event Free Survival
- Secondary Outcome Measures
Name Time Method Major haemorrhage Occurring while on treatment (over 3 years) As defined in the protocol
Transformation to PPV-MF Occurring while on treatment (over 3 years) Transformation to PPV-MF
Transformation to MDS and/or AML Occurring while on treatment (over 3 years) Transformation to MDS and/or AML
Symptom burden/Quality of life (MDASI) Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36 As measured via MDASI
Symptom burden/Quality of life (EQ-5D) Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36 As measured via EQ-5D
Health economics At the end of the trial (trial duration of approximately 8 years) Including cost utility and cost effectiveness analyses as defined by the protocol (e.g. QALYs)
Change in QRisk score Collected at baseline and years 1, 2 and 3 Change in QRisk score
Major thrombosis Occurring while on treatment (over 3 years) As defined in the protocol, combined and split to venous and arterial
Spleen response Response at 1 year post randomisation in patients with splenomegaly
Symptom burden/Quality of life (MPN-SAF) Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36 As measured via MPN-SAF
Complete Haematological remission (CHR) 1 year post-treatment As defined by ELN response criteria at 1 year
Peripheral blood JAK2 V617F allele burden At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation) According to ELN response criteria
Rates of discontinuation From treatment prior to protocol defined 3 years Trial discontinuation
Rate and severity of adverse events Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation)) collected according to CTCAE version 4.0 and the MITHRIDATE protocol
Time free from venesection Defined as the mean time between venesections while on trial treatment (treatment duration of 3 years) Time free from venesection
Secondary malignancy Occurring throughout the trial (from randomisation until approximately 3 years post-randomisation) Malignancy independent to the original diagnosis
Trial Locations
- Locations (47)
Royal United Hospital
🇬🇧Bath, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Southmead Hospital
🇬🇧Bristol, United Kingdom
Russells Hall Hospital
🇬🇧Dudley, United Kingdom
Kettering General Hospital
🇬🇧Kettering, United Kingdom
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
The James Cook University Hospital
🇬🇧Middlesbrough, United Kingdom
North Tyneside General Hospital
🇬🇧North Shields, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧Norwich, United Kingdom
Halton Hospital
🇬🇧Runcorn, United Kingdom
Wexham Park Hospital
🇬🇧Slough, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
St Richard's Hospital
🇬🇧Chichester, United Kingdom
Colchester Hospital
🇬🇧Colchester, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, United Kingdom
Calderdale Royal Hospital
🇬🇧Halifax, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, United Kingdom
Raigmore Hospital
🇬🇧Inverness, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
St John's Hospital
🇬🇧Livingston, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Royal Gwent Hospital
🇬🇧Newport, United Kingdom
Northampton General Hospital
🇬🇧Northampton, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Berkshire Hospital
🇬🇧Reading, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
Good Hope Hospital
🇬🇧Sutton Coldfield, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Warwick Hospital
🇬🇧Warwick, United Kingdom
Arrowe Park Hospital
🇬🇧Wirral, United Kingdom
Worthing Hospital
🇬🇧Worthing, United Kingdom