NCT05020652已完成2 期
A Randomized, Double Blind, Double Dummy, Parallel Controlled, Multicenter Phase II Clinical Trial of TQ05105 Tablets Versus Hydroxyurea Tablets in the Treatment of Moderate and High Risk Myelofibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 4
- 主要终点
- Spleen Volume was Reduced by more than 35% from baseline（SVR35） assessed by Independent Review Committee (IRC)
研究概览
简要总结
Q05105 tablet is a Janus kinase 2 (JAK2) inhibitor, which can be used to treat JAK2 target related diseases, such as moderate or high-risk multiple myelofibrosis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subjects volunteered to join the study and signed informed consent, with good compliance;
- •Age: 18-75 years old (when signing the informed consent form); Eastern Cooperative oncology Group (ECoG) Performance Status (PS) score: 0-2; The expected survival time is more than 24 weeks;
- •Primary Myelofibrosis (PMF) was diagnosed according to World Health Organization (WHO) standard (2016 Edition), or Post Polycythemia Vera(PV)-MF or Post Essential Thrombocythemia (ET)-MF was diagnosed according to International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) standard; JAK2 mutation or not was included in the study;
- •According to Dynamic International Prognostic Scoring System (DIPSS) prognosis grading criteria, the patients with myelofibrosis were assessed as medium risk (including medium risk-1, medium risk-2) or high risk;
- •Splenomegaly: palpate the splenic margin at least 5cm below the ribs (the distance from the costal margin to the farthest point of splenic protrusion);
- •Peripheral blood primordial cells ≤ 10%;
- •If antifibrotic treatment for myelofibrosis is ongoing before screening, hydroxyurea, any immunomodulators such as thalidomide, short-acting interferons, androgenic drugs, and any immunosuppressants (such as prednisone > 10mg/day or equivalent strength corticosteroids) must be discontinued for at least 2 weeks before randomization; long-acting interferons and erythropoietin must be discontinued for at least 4 weeks before randomization;
- •No growth factor, colony stimulating factor, thrombopoietin or platelet transfusion was received within 2 weeks before the examination, and hemoglobin (Hgb) ≥ 80g / L, platelet count (PLT) ≥ 100 within 7 days before the random date × 10^9 / L and neutrophil absolute value (neut) ≥ 1.0 × 10^9/L;
- •The main organs were functional 7 days before the random date, which was in accordance with the following criteria: Total Bilirubin (TBIL) was less than 2 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were less than 2.5 times of ULN; Serum creatinine (Cr) < 1.5 times of ULN or creatinine clearance rate (Ccr) ≥ 50ml/min; The blood coagulation function should be checked in accordance with: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR) < 1.5 × ULN (not anticoagulant treatment); Left ventricular ejection fraction (LVEF) evaluated by color Doppler ultrasonography ≥ 50%;
- •Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine device, contraceptive or condom) during the study period and within 6 months after the end of the study; The serum pregnancy test was negative within 7 days before the date of randomization and must be non lactating subjects; Male subjects should agree to use contraception during the study period and within 6 months after the end of the study period.
排除标准
- •Those who have received allogeneic stem cell transplantation in the past, or autologous stem cell transplantation within 3 months before the random date, or recently planned stem cell transplantation;
- •Patients who have received JAK inhibitors in the past;
- •Those who had undergone splenectomy or received splenic radiotherapy within 6 months before the date of randomization (including internal and external radiotherapy);
- •Other malignancies were present or present within 3 years before the date of randomization. The following two cases can be included: other malignant tumors treated by single operation have achieved 5-year disease-free survival (DFS) in a row; Cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];
- •Patients with multiple factors (such as inability to swallow, postoperative gastrointestinal resection, acute and chronic diarrhea, intestinal obstruction, etc.) affecting oral or absorption of drugs;
- •Non hematological toxicity caused by previous treatment did not return to ≤ 1 (excluding alopecia);
- •Patients who received major surgical treatment or had obvious traumatic injury within 4 weeks before the date of randomization;
- •At present, there are congenital bleeding or coagulation diseases, or are using anticoagulant therapy;
- •Arteriovenous thrombotic events occurred within 6 months before the random date, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism;
- •A history of psychotropic substance abuse or mental disorder;
- •Active or uncontrolled severe infection (≥ Common Terminology Criteria for Adverse Events(CTCAE)2 infection);
- •Hepatitis B Virus (HBV) DNA≥ULN； Hepatitis C antibody positive and Hepatitis C Virus (HCV) RNA ≥ ULN;
- •Myocardial ischemia or myocardial infarction, arrhythmia, QT interval prolongation (corrected QT interval (QTc) ≥ 450 ms for male, QTc ≥ 470 ms for female) and congestive heart failure (NYHA classification) of grade 2 or above;
- •Blood pressure control is not ideal (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
- •Renal failure requires hemodialysis or peritoneal dialysis;
- •Newly diagnosed pulmonary fibrosis or drug-related interstitial lung disease within 3 months before the date of randomization;
- •History of immunodeficiency, including Human Immunodeficiency Virus (HIV) positive or other acquired or congenital immunodeficiency diseases, or organ transplantation;
- •Patients with epilepsy and need treatment;
- •Within 4 weeks prior to the random date, the patient had received chemotherapy, radiotherapy or other anti-cancer treatments (except as stipulated in item 7 of the inclusion criteria);
- •Within 2 weeks before the date of randomization, he received Chinese patent medicines (including compound cantharis capsule, Kang'ai injection, kang'laite capsule / injection, Aidi injection, Brucea javanica oil injection / capsule, Xiaoaiping tablet / injection, cinobufagin capsule, etc.) with anti-tumor indications specified in nmpa approved drug instructions;
- •Uncontrolled pleural effusion, pericardial effusion or ascites;
- •Patients with central nervous system involvement;
- •There was a history of live attenuated vaccine inoculation within 4 weeks before the date of randomization or live attenuated vaccine inoculation was planned during the study period;
研究组 & 干预措施
TQ05105 tablets + Hydroxyurea blank tablets
Experimental
Take TQ05105 Tablets + Hydroxyurea blank tablets orally on an empty stomach, with an interval of at least 8 hours, and the best interval is 12 hours. Every 4 weeks is a period of administration
干预措施: TQ05105 tablets (Drug)
TQ05105 blank tablets + Hydroxyurea tablets
Active Comparator
Take TQ05105 blank tablets + Hydroxyurea tablets orally on an empty stomach, with an interval of at least 8 hours, and the best interval is 12 hours. Every 4 weeks is a period of administration
干预措施: Hydroxycarbamide tablets (Drug)
结局指标
主要结局
Spleen Volume was Reduced by more than 35% from baseline（SVR35） assessed by Independent Review Committee (IRC)
时间窗: up to 24 weeks
Proportion of subjects whose spleen volume was reduced by more than 35% from baseline at the end of week 24 of IRC assessment (SVR35)
次要结局
- Progression-free survival (PFS)(up to 120 weeks)
- Leukemia free survival (LFS)(up to 120 weeks)
- Overall survival (OS)(up to 120 weeks)
- SVR35 assessed by the researchers and objective response rate (ORR)(up to 24 weeks)
- The incidence and severity of adverse events (AEs) occurred during the study(up to 120 weeks)
- optimal response rate of splenic response(up to 120 weeks)
- onset time of splenic response(up to 120 weeks)
- the proportion of subjects whose total symptom score of Myeloproliferative neoplasm- Symptom Assessment Form- Total Symptom Score(MPN-SAF TSS) decreased by more than 50% compared with baseline(up to 24 weeks)
- The total symptom score of MPN-SAF TSS decreased compared with baseline(up to 24 weeks)
- Duration of Maintenance of a Least 35% Reduction in Spleen Volume(DoMSR)(up to 120 weeks)
研究者
研究点 (4)
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