NCT06122831招募中1 期
A Phase Ib/II Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Intermediate- and High-risk Myelofibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 22
- 主要终点
- Maximal tolerance dose (MTD)
研究概览
简要总结
This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy and safety of TQ05105 Tablets combined with TQB3617 Capsules in patients with intermediate- and high-risk Myelofibrosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary and signed informed consent, good compliance.
- •Age: 18 or above (when signing the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 2; Life expectancy ≥ 24 weeks.
- •Patients diagnosed with Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post PV MF), or post essential thrombocythemia myelofibrosis (post ET MF)
- •According to the dynamic international prognostic scoring system (DIPSS), patients with intermediate or high risk of bone marrow fibrosis were evaluated.
- •Patients with poor efficacy of JAK inhibitors (for phase Ib and phase II cohort 2)
- •Patients who had not received JAK inhibitor treatment (for phase II cohort 1).
- •Spleen enlargement.
- •Peripheral blood primary cells and bone marrow primary cells were ≤10%.
- •No growth factor, colony stimulating factor, thrombopoietin or platelet transfusion was received within 2 weeks before the examination, and the blood routine indexes met the requirements within 7 days before the first administration.
- •The Main organ function is normal.
- •Men and women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study. Serum human chorionic gonadotrophin (HCG) test is not negative within 7 days before the first administration and must be non-lactating patients.
排除标准
- •Patients who have previously received allogeneic stem cell transplantation, or received autologous stem cell transplantation within 3 months before the first administration, or recently planned stem cell transplantation;
- •Previous treatment with BET inhibitors;
- •Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
- •Use of any MF medications, any immunomodulators, androgens, any immunosuppressive agents, erythropoietin, aspirin > 100 mg/day within 2 weeks prior to first administration;
- •Other malignancies within 3 years prior to first administration or currently present.
- •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;
- •Major surgical treatment or significant traumatic injury within 4 weeks prior to first administration;
- •Presence of congenital bleeding disorder and congenital coagulopathy;
- •Patients who had arterial/venous thrombosis events within 6 months before the first administration.
- •Have a history of mental drug abuse, or have a mental disorder.
- •Active or uncontrolled severe infection;
- •Active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection and HCV RNA positive, or active Corona Virus Disease 2019 (COVID-19) infection;
- •Patients with grade III or above congestive heart failure, unstable angina pectoris or myocardial infarction, or arrhythmia requiring treatment, or QT interval prolongation within 6 months before the first administration;
- •Unsatisfactory blood pressure control despite standard therapy;
- •Patients with renal failure requiring hemodialysis or peritoneal dialysis;
- •Patients newly diagnosed with pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before the first administration;
- •Patients with a history of immunodeficiency disease or organ transplantation;
- •Patients with epilepsy requiring treatment;
- •Patients who have received Chinese patent medicines with anti-tumor indications specified in the approved drug package insert of China National Medical Products Administration (NMPA) within 2 weeks before the first administration;
- •Patients with uncontrolled pleural effusion, pericardial effusion or ascites;
- •There was a history of attenuated live vaccine inoculation within 4 weeks before the first administration, or attenuated live vaccine inoculation was planned during the study period.
- •People with known hypersensitivity to the study drug and excipients;
- •Patients diagnosed as active autoimmune diseases within 2 years before the first administration;
- •Those who participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration (except JAK inhibitor-related clinical trials).
- •According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.
研究组 & 干预措施
TQ05105 Tablets + TQB3617 Capsules
Experimental
TQ05105 Tablets combined with TQB3617 Capsules, orally administered. 21 days as a treatment cycle.
TQB3617 Capsules, orally administered, 21 days as a treatment cycle.
干预措施: TQ05105 Tablets (Drug)
TQ05105 Tablets + TQB3617 Capsules
Experimental
TQ05105 Tablets combined with TQB3617 Capsules, orally administered. 21 days as a treatment cycle.
TQB3617 Capsules, orally administered, 21 days as a treatment cycle.
干预措施: TQB3617 Capsules (Drug)
结局指标
主要结局
Maximal tolerance dose (MTD)
时间窗: Up to 2 years.
If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD.
Recommended phase II dose (RP2D)
时间窗: Up to 2 years
The RP2D is defined as the lower dose level to MTD based on the safety profile.
≥35% reduction in spleen volume (SVR35)
时间窗: Up to 24 weeks
The proportion of subjects with a ≥35% reduction in spleen volume from baseline at the end of treatment at week 24.
次要结局
- SVR35(Up to 120 weeks)
- Optimum effective rate(Up to 120 weeks)
- Onset time of splenic response(Up to 120 weeks)
- Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR)(Up to 120 weeks)
- Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)(Up to 60 weeks)
- MPN-SAF TSS change(Up to 120 weeks)
- The proportion of subjects with gene mutation achieving SVR35(Up to 48 weeks)
- Progression-free survival (PFS)(Up to 120 weeks)
- Variant allele frequency (VAF)(Up to 48 weeks)
- Incidence of adverse events (AEs)(Baseline up to 120 weeks)
- The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50%(Up to 48 weeks.)
- Leukemia free survival (LFS)(Up to 120 weeks)
- Overall Survival (OS)(Up to 120 weeks)
- Severity of adverse events (AEs)(Baseline up to 120 weeks)
研究者
研究点 (22)
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