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Polycythemia VeraPhase 3MITHRIDATENCT04116502

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

A Phase 3 study testing Ruxolitinib, Hydroxycarbamide and Interferon-Alpha in people with Polycythemia Vera, run by University of Birmingham at 55 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Polycythemia Vera
What is being tested?
Ruxolitinib, Hydroxycarbamide and Interferon-Alpha
Could I receive a placebo?
No, everyone receives an active treatment
How many people
586 participants
Where
55 sitesUnited Kingdom
Study dates
25 Oct 2019to 1 Apr 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 24Show fewer
  • 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

Trial locations and contacts

55 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Natalia Morelli contact

+44(0)121 414 2535

mithridate@trials.bham.ac.uk

55 sites in 1 country

United Kingdom55 sites, 53 recruiting

  • Aberdeen Royal Infirmary

    Aberdeen, AB25 2ZN

    Recruiting

  • Royal United Hospital

    Bath, BA1 3NG

    Recruiting

  • Belfast City Hospital

    Belfast, BT9 7AB

    Recruiting

  • Birmingham Heartlands Hospital

    Birmingham, B9 5SS

    Recruiting

  • Blackpool Victoria Hospital

    Blackpool, FY3 8NR

    Recruiting

  • Glan Clwyd Hospital

    Bodelwyddan, LL18 5UJ

    Recruiting

  • Royal Bournemouth Hospital

    Bournemouth, BH7 7DW

    Recruiting

  • Southmead Hospital

    Bristol, BS10 5NB

    Recruiting

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

    Recruiting

  • Kent and Canterbury Hospital

    Canterbury, CT1 3NG

    Recruiting

  • University Hospital of Wales

    Cardiff, CF14 4XW

    Recruiting

  • St Richard's Hospital

    Chichester, PO19 6SE

    Recruiting

  • Colchester Hospital

    Colchester, CO4 5JL

    Recruiting

  • Castle Hill Hospital

    Cottingham, HU16 5JQ

    Recruiting

  • University Hospital

    Coventry, CV2 2DX

    Recruiting

  • Russells Hall Hospital

    Dudley, DY1 2HQ

    Recruiting

  • Western General Hospital

    Edinburgh, EH4 2XU

    Recruiting

  • Royal Devon and Exeter Hospital

    Exeter, EX2 5DW

    Recruiting

  • Gloucestershire Royal Hospital

    Gloucester, GL1 3NN

    Recruiting

  • Calderdale Royal Hospital

    Halifax, HX3 0PW

    Active, not recruiting

  • Huddersfield Royal Infirmary

    Huddersfield, HD3 3EA

    Active, not recruiting

  • Raigmore Hospital

    Inverness, IV2 3UJ

    Recruiting

  • Ipswich Hospital

    Ipswich, IP4 5PD

    Recruiting

  • Kettering General Hospital

    Kettering, NN16 8UZ

    Recruiting

  • St James's University Hospital

    Leeds, LS9 7TF

    Recruiting

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

    Recruiting

  • St John's Hospital

    Livingston, EH54 6PP

    Recruiting

  • University College Hospital

    London, NW1 2BU

    Recruiting

  • Guy's Hospital

    London, SE1 9RT

    Recruiting

  • St George's Hospital

    London, SW17 0QT

    Recruiting

  • Wythenshawe Hospital

    Manchester, M23 9LT

    Recruiting

  • Arrowe Park Hospital

    Metropolitan Borough of Wirral, CH49 5PE

    Recruiting

  • The James Cook University Hospital

    Middlesbrough, TS4 3BW

    Recruiting

  • Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

    Recruiting

  • Royal Gwent Hospital

    Newport, NP20 2UB

    Recruiting

  • North Tyneside General Hospital

    North Shields, NE29 8NH

    Recruiting

  • Northampton General Hospital

    Northampton, NN1 5BD

    Recruiting

  • Norfolk and Norwich University Hospital

    Norwich, NR4 7UY

    Recruiting

  • Nottingham City Hospital

    Nottingham, NG5 1PB

    Recruiting

  • George Eliot Hospital

    Nuneaton, CV10 7DJ

    Recruiting

  • Churchill Hospital

    Oxford, OX3 7LE

    Recruiting

  • Derriford Hospital

    Plymouth, PL6 8DH

    Recruiting

  • Royal Berkshire Hospital

    Reading, RG1 5AN

    Recruiting

  • Halton Hospital

    Runcorn, WA7 2DA

    Recruiting

  • Royal Hallamshire Hospital

    Sheffield, S10 2JF

    Recruiting

  • Wexham Park Hospital

    Slough, SL2 4HL

    Recruiting

  • Southampton General Hospital

    Southampton, SO16 6YD

    Recruiting

  • Royal Stoke University Hospital

    Stoke-on-Trent, ST4 6QG

    Recruiting

  • Sunderland Royal Hospital

    Sunderland, SR4 7TP

    Recruiting

  • Good Hope Hospital

    Sutton Coldfield, B75 7RR

    Recruiting

  • Royal Cornwall Hospital

    Truro, TR1 3LJ

    Recruiting

  • Warwick Hospital

    Warwick, CV34 5BW

    Recruiting

  • New Cross Hospital

    Wolverhampton, WV10 0QP

    Recruiting

  • Worthing Hospital

    Worthing, BN11 2DH

    Recruiting

  • York Hospital

    York, YO31 8HE

    Recruiting

Other trials in United Kingdom

About this study

Official title: 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

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.

Read the 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.

Being tested
Ruxolitinib, Hydroxycarbamide, Interferon-Alpha
Medical subject headings
Polycythemia Vera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RuxolitinibDrug

    Also called Jakavi®

    10mg of ruxolitinib twice daily (bd)

  • HydroxycarbamideDrug

    Also called Hydroxyurea

    Via standard hospital mechanisms

  • Interferon-AlphaDrug

    Also called Interferon, alpha interferon, Intron® A, Roferon® A

    Any formulation, via standard hospital mechanisms

Study groups in NCT04116502
Study groupRoleWhat they receive
A- RuxolitinibExperimentalTreatment with Ruxolitinib
Receives: Drug: Ruxolitinib
B- Hydroxycarbamide OR Interferon AActive comparatorBest Available Therapy (BAT), Treatment with hydroxycarbamide OR Interferon A
Receives: Drug: Hydroxycarbamide; Drug: Interferon-Alpha

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event Free Survival (EFS)

    Event Free Survival

    Measured: 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

Secondary outcomes (16)

  1. Major thrombosis

    As defined in the protocol, combined and split to venous and arterial

    Measured: Occurring while on treatment (over 3 years)

  2. Major haemorrhage

    As defined in the protocol

    Measured: Occurring while on treatment (over 3 years)

  3. Transformation to PPV-MF

    Transformation to PPV-MF

    Measured: Occurring while on treatment (over 3 years)

  4. Transformation to MDS and/or AML

    Transformation to MDS and/or AML

    Measured: Occurring while on treatment (over 3 years)

  5. Complete Haematological remission (CHR)

    As defined by ELN response criteria at 1 year

    Measured: 1 year post-treatment

  6. Symptom burden/Quality of life (MPN-SAF)

    As measured via MPN-SAF

    Measured: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

  7. Symptom burden/Quality of life (MDASI)

    As measured via MDASI

    Measured: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

  8. Symptom burden/Quality of life (EQ-5D)

    As measured via EQ-5D

    Measured: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

  9. Health economics

    Including cost utility and cost effectiveness analyses as defined by the protocol (e.g. QALYs)

    Measured: At the end of the trial (trial duration of approximately 8 years)

  10. Peripheral blood JAK2 V617F allele burden

    According to ELN response criteria

    Measured: At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation)

  11. Rates of discontinuation

    Trial discontinuation

    Measured: From treatment prior to protocol defined 3 years

  12. Rate and severity of adverse events

    collected according to CTCAE version 4.0 and the MITHRIDATE protocol

    Measured: Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation))

  13. Spleen response

    in patients with splenomegaly

    Measured: Response at 1 year post randomisation

  14. Time free from venesection

    Time free from venesection

    Measured: Defined as the mean time between venesections while on trial treatment (treatment duration of 3 years)

  15. Secondary malignancy

    Malignancy independent to the original diagnosis

    Measured: Occurring throughout the trial (from randomisation until approximately 3 years post-randomisation)

  16. Change in QRisk score

    Change in QRisk score

    Measured: Collected at baseline and years 1, 2 and 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2019
  2. Study start25 Oct 2019
  3. Primary completion31 Oct 2028 (estimated)
  4. Study completion1 Apr 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
586 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04116502
Sponsor's protocol ID
RG_16-148
Acronym
MITHRIDATE
Status last verified
Apr 2026
First submitted
9 Sep 2019
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ruxolitinib, Hydroxycarbamide and Interferon-Alpha in people with Polycythemia Vera, run by University of Birmingham at 55 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Natalia Morelli (+44(0)121 414 2535, mithridate@trials.bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival (EFS) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04116502.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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