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Recruiting NCT04116502

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

Phase III Interventional Polycythemia Vera

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Ruxolitinib, Hydroxycarbamide, Interferon-Alpha.
Who it may be relevant to
Registry conditions: Polycythemia Vera. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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.

Interventions

  • Drug Ruxolitinib
    10mg of ruxolitinib twice daily (bd)
  • Drug Hydroxycarbamide
    Via standard hospital mechanisms
  • Drug Interferon-Alpha
    Any formulation, via standard hospital mechanisms

Primary outcome measures

  • 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]
Secondary outcome measures (12)
  • Major thrombosis [Time frame: Occurring while on treatment (over 3 years)]
  • Major haemorrhage [Time frame: Occurring while on treatment (over 3 years)]
  • Transformation to PPV-MF [Time frame: Occurring while on treatment (over 3 years)]
  • Transformation to MDS and/or AML [Time frame: Occurring while on treatment (over 3 years)]
  • Complete Haematological remission (CHR) [Time frame: 1 year post-treatment]
  • Symptom burden/Quality of life (MPN-SAF) [Time frame: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36]
  • Symptom burden/Quality of life (MDASI) [Time frame: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36]
  • Symptom burden/Quality of life (EQ-5D) [Time frame: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36]
  • Health economics [Time frame: At the end of the trial (trial duration of approximately 8 years)]
  • Peripheral blood JAK2 V617F allele burden [Time frame: At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation)]
  • Rates of discontinuation [Time frame: From treatment prior to protocol defined 3 years]
  • Rate and severity of adverse events [Time frame: Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation))]

Eligibility criteria

Population:

High risk PV defined as WBC >11 x 10\^9/l\* AND at least ONE of the following

  • Age >60 years
  • Prior thrombosis or haemorrhage
  • Platelet count >1000 x 10\^9/l\*
  • Hypertension or diabetes requiring pharmacological therapy (\*At any time since diagnosis)

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

United Kingdom · 47 centers
  • Aberdeen Royal Infirmary — Aberdeen
  • Royal United Hospital — Bath
  • Belfast City Hospital — Belfast
  • Birmingham Heartlands Hospital — Birmingham
  • Blackpool Victoria Hospital — Blackpool
  • Royal Bournemouth Hospital — Bournemouth
  • Southmead Hospital — Bristol
  • Addenbrooke's Hospital — Cambridge
  • … and 39 more centers

Identifiers

NCT: NCT04116502 · RG_16-148

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗