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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Ruxolitinib | Jakavi® | A- Ruxolitinib |
| Hydroxycarbamide | Hydroxyurea | B- Hydroxycarbamide OR Interferon A |
| Interferon-Alpha | Interferon, alpha interferon, Intron® A, Roferon® A | B- 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
| Name | Type | Description | Interventions |
|---|
| A- Ruxolitinib | Experimental | Treatment with Ruxolitinib | |
| B- Hydroxycarbamide OR Interferon A | Active Comparator | Best 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 30, 2020
