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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Event Free Survival (EFS) [Срок оценки: 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]

Вторичные конечные точки (12)

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

Критерии участия

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)

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 47 центров

• 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
• … и ещё 39 центров

Идентификаторы

NCT: NCT04116502 · RG_16-148

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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