2024-516109-21-00招募中3 期
MITHRIDATE: 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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 293
- 试验地点
- 35
- 主要终点
- 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.
研究概览
简要总结
To compare the time to combined incidence of; major thrombosis, major haemorrhage, death, transformation to Myelodysplastic syndrome, Acute Myeloid Leukaemia, or post-PV (PPV) Myelofibrosis in high risk PV patients randomised to ruxolitinib versus best available therapy.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patient ≥ 18 years of age
- •Diagnosis of PV meeting WHO criteria within past 15 years
- •Meets criteria of high risk PV (High risk PV defined as WBC >11 x 109/l* AND at least ONE of the following • Age >60 years • Prior thrombosis or major haemorrhage related to disease • Platelet count >1000 x 109/l* • Hypertension or diabetes requiring pharmacological therapy. *At any time since diagnosis)
- •Patients must have a screening haemoglobin of >8g/dl
- •Patients may have received antiplatelet agents and venesection
- •Patients may have received ONE or less cytoreductive therapy for less than 10 years (BUT they should not be resistant or intolerant to that therapy)
- •Able to provide written informed consent
排除标准
- •Diagnosis of PV > 15 years previously
- •Unable to give informed consent
- •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 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 galactose intolerance, total lactase deficiency or glucose- galactose malabsorption
- •Patients with uncontrolled neuropsychiatric disorders
- •Patients with uncontrolled cutaneous cancers
- •All women of childbearing potential (as per Appendix 8 definition) FRANCE ONLY
- •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
- •No affiliation with the French healthcare system FRANCE ONLY
- •Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up FRANCE ONLY
- •Patients deprived of their liberty by a judicial or administrative decision FRANCE ONLY
- •Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice) FRANCE ONLY
- •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
结局指标
主要结局
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.
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.
次要结局
- 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
- Exploratory 1: Progression of marrow fibrosis
- Exploratory 2: Impact of the treatment on molecular signatures of disease
- Exploratory 3. Clonal involvement within the stem/progenitor cell compartment
- Exploratory 4. Clonal evolution (acquisition of additional mutations)
- Exploratory 5. Reduction of peripheral blood allele burden of other disease-associated mutations
- Exploratory 6. Assessment of the prevalence of clonality markers for haematological disease and any change over time
- Exploratory 7. Correlation of thrombosis biomarkers with clinical thrombosis events
- Exploratory Metabolic: 1. Cardiac event (angina, acute coronary syndrome, acute MI; arrhythmia)
- Exploratory Metabolic 2. Pulmonary hypertension
- Exploratory Metabolic 3. Coronary intervention: e.g. angiogram, angioplasty, CABG
- Exploratory Metabolic 4. Deterioration in cardiac function e.g. LVEF% on ECHO/ MUGA and/or NYHA classification
- Exploratory Metabolic 7. Venous thrombosis including DVT, PE, Cerebral, splanchnic, other
- Exploratory Metabolic 8. Pregnancy loss
- Exploratory Metabolic 5. Cerebrovascular event (TIA, haemorrhagic CVA, non-haemorrhagic CVA)
- Exploratory Metabolic 6. Arterial vascular event (peripheral vascular disease: claudication, carotid stenosis)
研究者
Clinical Trial Coordinator
Scientific
The University Of Birmingham
研究点 (35)
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