Clinical Trials /

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

NCT04116502

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.

Related Conditions:
  • Polycythemia Vera
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polcythemia Vera
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RG_16-148
  • NCT ID: NCT04116502

Conditions

  • Polycythemia Vera

Interventions

DrugSynonymsArms
RuxolitinibJakavi®A- Ruxolitinib
HydroxycarbamideHydroxyureaB- Hydroxycarbamide OR Interferon A
Interferon-AlphaInterferon, alpha interferon, Intron® A, Roferon® AB- Hydroxycarbamide OR Interferon A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
A- RuxolitinibExperimentalTreatment with Ruxolitinib
  • Ruxolitinib
B- Hydroxycarbamide OR Interferon AActive ComparatorBest Available Therapy (BAT), Treatment with hydroxycarbamide OR Interferon A
  • Hydroxycarbamide
  • Interferon-Alpha

Eligibility Criteria

        Population:

        High risk PV defined as WBC >11 x 109/l* AND at least ONE of the following

          -  Age >60 years

          -  Prior thrombosis or haemorrhage

          -  Platelet count >1000 x 109/l*

               -  At any time since diagnosis

        Inclusion Criteria:

          1. Patient ≥18 years of age

          2. Diagnosis of PV meeting the WHO criteria within the past 10 years

          3. Meets criteria of high risk* PV (see above for specific population)

          4. Patients may have received antiplatelet agents and venesection

          5. Patients may have received ONE cytoreductive therapy for PV less than 5 years (BUT
             they should not be resistant or intolerant to that therapy)

          6. Able to provide written informed consent

        Exclusion Criteria:

          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

         15. Unable to give informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event Free Survival (EFS)
Time Frame:the time from randomisation to the date of the first major thrombosis/haemorrhage, death,transformation to Myelodisplastic Syndromes, Acute Myeloid Leukaemia or Post-polycythemia Vera Myelofibrosis, if within the ~3 year trial period
Safety Issue:
Description:Event Free Survival

Secondary Outcome Measures

Measure:Major thrombosis
Time Frame:Occuring while on treatment (over 3 years)
Safety Issue:
Description:As defined in the protocol, combined and split to venous and arterial
Measure:Major haemorrhage
Time Frame:Occuring while on treatment (over 3 years)
Safety Issue:
Description:As defined in the protocol
Measure:Transformation to PPV-MF
Time Frame:Occuring while on treatment (over 3 years)
Safety Issue:
Description:Transformation to PPV-MF
Measure:Transformation to MDS and/or AML
Time Frame:Occuring while on treatment (over 3 years)
Safety Issue:
Description:Transformation to MDS and/or AML
Measure:Complete Haematological remission (CHR)
Time Frame:1 year post-treatment
Safety Issue:
Description:As defined by ELN response criteria at 1 year
Measure: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
Safety Issue:
Description:As measured via MPN-SAF
Measure:Symptom burden/Quality of life (MDASI)
Time Frame:Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36
Safety Issue:
Description:As measured via MDASI
Measure: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
Safety Issue:
Description:As measured via EQ-5D
Measure:Health economics
Time Frame:At the end of the trial (trial duration of approximately 8 years)
Safety Issue:
Description:Including cost utility and cost effectiveness analyses as defined by the protocol (e.g. QALYs)
Measure:Peripheral blood JAK2 V617F allele burden
Time Frame:At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation)
Safety Issue:
Description:According to ELN response criteria
Measure:Rates of discontinuation
Time Frame:From treatment prior to protocol defined 3 years
Safety Issue:
Description:Trial discontinuation
Measure:Rate and severity of adverse events
Time Frame:Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation))
Safety Issue:
Description:collected according to CTCAE version 4.0 and the MITHRIDATE protocol
Measure:Spleen response
Time Frame:Response at 1 year post randomisation
Safety Issue:
Description:in patients with splenomegaly
Measure:Time free from venesection
Time Frame:Defined as the mean time between venesections while on trial treatment (treatment duration of 3 years)
Safety Issue:
Description:Time free from venesection
Measure:Secondary malignancy
Time Frame:Occuring throughout the trial (from randomisation until approximately 3 years post-randomisation)
Safety Issue:
Description:Malignancy independent to the original diagnosis
Measure:Change in QRisk score
Time Frame:Collected at baseline and years 1, 2 and 3
Safety Issue:
Description:Change in QRisk score

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Birmingham

Last Updated

March 27, 2020