E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myeloproliferative neoplasm (MPN), specifically Polycythaemia Vera |
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E.1.1.1 | Medical condition in easily understood language |
Disease of the bone marrow in which excess red blood cells are produced |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the time to combined incidence of; major thrombosis, major haemorrhage, death or transformation to MDS, AML or post-PV (PPV) MF in high risk PV patients randomised to ruxolitinib versus standard care. |
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E.2.2 | Secondary objectives of the trial |
To compare the incidence of major thrombosis, major haemorrhage and transformation to PPV MF in high-risk PV patients receiving ruxolitinib or best available therapy (HC). To compare the incidence of transformation to MDS and/or AML and complete haematological response (CHR) between best available therapy and ruxolitinib. To determine the rates of discontinuation from treatment and the rate and severity of adverse events in both treatment groups. To compare spleen response and time free from venesection in both of the treatment groups. To compare the incidence of secondary malignancy and the change in QRisk in both treatment groups.
Exploratory Objectives.
Exploratory Metabolic Objectives.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient ≥18 years of age - Diagnosis of PV meeting the WHO criteria within the past 10 years - Meets criteria of high risk* PV (see above for specific population) - Patients may have received antiplatelet agents and venesection - Patients may have received ONE or less cytoreductive therapy for PV less than 5 years (BUT they should not be resistant or intolerant to that therapy) - Able to provide written informed consent |
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E.4 | Principal exclusion criteria |
- Diagnosis of PV > 10 years previously - Absence of any 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 5 years OR resistance/intolerance to that therapy - Active infection including hepatitis B, hepatitis C, 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 and partners of childbearing potential 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 ml/min - Unable to give informed consent Moreover French specific criteria: - Legal protection (i.e., guardianship, curator or incarceration) No affiliation with the French health care system
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E.5 End points |
E.5.1 | Primary end point(s) |
Event Free Survival (EFS): defined as the time from randomisation to the date of the first event including; • Major thrombosis, • Major haemorrhage, • Death • Transformation to MDS, AML or PPV-MF. Patients who do not experience an event during the trial will be censored at their date last seen.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 32 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |