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

NCT04116502 | Recruiting Phase 3 DMC

• 1 other identifier: RG_16-148
• Study Type: interventional
• Target: 586
• Locations: 1 country
• Sites: 47

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.

Conditions

Polycythemia Vera

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS)

  Event Free Survival

  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)

• Major thrombosis

  Occurring while on treatment (over 3 years)

• Major haemorrhage

  Occurring while on treatment (over 3 years)

• Transformation to PPV-MF

  Occurring while on treatment (over 3 years)

• Transformation to MDS and/or AML

  Occurring while on treatment (over 3 years)

• Complete Haematological remission (CHR)

  1 year post-treatment

Other Outcomes (15)

• Progression of marrow fibrosis

  Occurring throughout the trial (from randomisation to approximately 3 years post-randomisation)

• Impact of treatment on molecular signatures of disease

  Occurring throughout the trial (from randomisation to approximately 3 years post-randomisation)

• Clonal involvement

  Occurring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Study Arms (2)

A- Ruxolitinib

EXPERIMENTAL

Treatment with Ruxolitinib

Drug: Ruxolitinib

B- Hydroxycarbamide OR Interferon A

ACTIVE COMPARATOR

Best Available Therapy (BAT), Treatment with hydroxycarbamide OR Interferon A

Drug: Hydroxycarbamide; Drug: Interferon-Alpha

Interventions

Ruxolitinib DRUG

10mg of ruxolitinib twice daily (bd)

Also known as: Jakavi®

A- Ruxolitinib

Hydroxycarbamide DRUG

Via standard hospital mechanisms

Also known as: Hydroxyurea

B- Hydroxycarbamide OR Interferon A

Interferon-Alpha DRUG

Any formulation, via standard hospital mechanisms

Also known as: Interferon, alpha interferon, Intron® A, Roferon® A

B- Hydroxycarbamide OR Interferon A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Birmingham: lead
• Novartis: collaborator
• MPN Voice: collaborator
• French National Cancer Institute (Institut National Du Cancer - France): collaborator

Study Sites (47)

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

RECRUITING

Royal United Hospital

Bath, BA1 3NG, United Kingdom

RECRUITING

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

RECRUITING

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

RECRUITING

Blackpool Victoria Hospital

Blackpool, FY3 8NR, United Kingdom

RECRUITING

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

RECRUITING

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Kent and Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

RECRUITING

St Richard's Hospital

Chichester, PO19 6SE, United Kingdom

RECRUITING

Colchester Hospital

Colchester, CO4 5JL, United Kingdom

RECRUITING

Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

RECRUITING

Russells Hall Hospital

Dudley, DY1 2HQ, United Kingdom

RECRUITING

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

RECRUITING

Gloucestershire Royal Hospital

Gloucester, GL1 3NN, United Kingdom

RECRUITING

Calderdale Royal Hospital

Halifax, HX3 0PW, United Kingdom

ACTIVE NOT RECRUITING

Huddersfield Royal Infirmary

Huddersfield, HD3 3EA, United Kingdom

ACTIVE NOT RECRUITING

Raigmore Hospital

Inverness, IV2 3UJ, United Kingdom

RECRUITING

Kettering General Hospital

Kettering, NN16 8UZ, United Kingdom

RECRUITING

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

St John's Hospital

Livingston, EH54 6PP, United Kingdom

RECRUITING

University College Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

St George's Hospital

London, SW17 0QT, United Kingdom

RECRUITING

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

RECRUITING

Arrowe Park Hospital

Metropolitan Borough of Wirral, CH49 5PE, United Kingdom

RECRUITING

The James Cook University Hospital

Middlesbrough, TS4 3BW, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Royal Gwent Hospital

Newport, NP20 2UB, United Kingdom

RECRUITING

North Tyneside General Hospital

North Shields, NE29 8NH, United Kingdom

RECRUITING

Northampton General Hospital

Northampton, NN1 5BD, United Kingdom

RECRUITING

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

Royal Berkshire Hospital

Reading, RG1 5AN, United Kingdom

RECRUITING

Halton Hospital

Runcorn, WA7 2DA, United Kingdom

RECRUITING

Wexham Park Hospital

Slough, SL2 4HL, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

RECRUITING

Sunderland Royal Hospital

Sunderland, SR4 7TP, United Kingdom

RECRUITING

Good Hope Hospital

Sutton Coldfield, B75 7RR, United Kingdom

RECRUITING

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

RECRUITING

Warwick Hospital

Warwick, CV34 5BW, United Kingdom

RECRUITING

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

RECRUITING

Worthing Hospital

Worthing, BN11 2DH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Polycythemia Vera

Interventions

ruxolitinib; Hydroxyurea; Interferon-alpha; Interferons

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Interferon Type I; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Claire Harrison

  Acting on behalf of the Sponsor (UK), Guy's Hospital, London, UK, SE1 9RT

  PRINCIPAL INVESTIGATOR

• Jean-Jacques Kiladjian

  (France) Clinical Investigations Center, Saint-Louis Hospital, Paris, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alex Hainsworth

CONTACT

+44(0)121 414 2535; mithridate@trials.bham.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: October 4, 2019
• Study Start: October 25, 2019
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (47)