Moderate and High Risk Myelofibrosis
Conditions
Brief summary
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
Interventions
DRUGTQ05105 tablets
TQ05105 tablet is a JAK2 inhibitor, which can be used to treat JAK2 target related diseases, such as moderate or high-risk multiple myelofibrosis.
Hydroxycarbamide tablet is a nucleoside diphosphate reductase inhibitor.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subjects volunteered to join the study and signed informed consent, with good compliance; 2. 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; 3. 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; 4. 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; 5. Splenomegaly: palpate the splenic margin at least 5cm below the ribs (the distance from the costal margin to the farthest point of splenic protrusion); 6. Peripheral blood primordial cells ≤ 10%; 7. 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; 8. 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; 9. 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%; 10. 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.
Exclusion criteria
1. 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; 2. Patients who have received JAK inhibitors in the past; 3. Those who had undergone splenectomy or received splenic radiotherapy within 6 months before the date of randomization (including internal and external radiotherapy); 4. 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 \[ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\]; 5. 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; 6. Non hematological toxicity caused by previous treatment did not return to ≤ 1 (excluding alopecia); 7. Patients who received major surgical treatment or had obvious traumatic injury within 4 weeks before the date of randomization; 8. At present, there are congenital bleeding or coagulation diseases, or are using anticoagulant therapy; 9. 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; 10. A history of psychotropic substance abuse or mental disorder; 11. Active or uncontrolled severe infection (≥ Common Terminology Criteria for Adverse Events(CTCAE)2 infection); 12. Hepatitis B Virus (HBV) DNA≥ULN； Hepatitis C antibody positive and Hepatitis C Virus (HCV) RNA ≥ ULN; 13. 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; 14. Blood pressure control is not ideal (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); 15. Renal failure requires hemodialysis or peritoneal dialysis; 16. Newly diagnosed pulmonary fibrosis or drug-related interstitial lung disease within 3 months before the date of randomization; 17. History of immunodeficiency, including Human Immunodeficiency Virus (HIV) positive or other acquired or congenital immunodeficiency diseases, or organ transplantation; 18. Patients with epilepsy and need treatment; 19. 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); 20. 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; 21. Uncontrolled pleural effusion, pericardial effusion or ascites; 22. Patients with central nervous system involvement; 23. 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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spleen Volume was Reduced by more than 35% from baseline（SVR35） assessed by Independent Review Committee (IRC) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| optimal response rate of splenic response | up to 120 weeks | Proportion of subjects with at least one reduction in spleen volume ≥ 35% from baseline. |
| onset time of splenic response | up to 120 weeks | The time between the date of randomization and the date when the spleen volume decreased ≥ 35% from the baseline for the first time. |
| Duration of Maintenance of a Least 35% Reduction in Spleen Volume(DoMSR) | up to 120 weeks | Duration of spleen volume reduction ≥ 35% from baseline (domsr): the time between the date when the spleen volume reduction ≥ 35% from baseline occurs for the first time and the date when the spleen volume reduction \< 35% from baseline. |
| 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 | At the 24th week, the proportion of subjects whose total symptom score of MPN-SAF TSS) decreased by more than 50% compared with baseline. |
| SVR35 assessed by the researchers and objective response rate (ORR) | up to 24 weeks | Proportion of subjects whose spleen volume was reduced by more than 35% from baseline to the end of the 24th week assessed by the researchers and ORR |
| Progression-free survival (PFS) | up to 120 weeks | The interval from the random date to the date of occurrence of any of the following events, whichever occurs first: ① the spleen volume increases by ≥ 25% compared with the lowest value during the treatment period (including the screening period); ② Death from any cause; ③ Start other anti-MF treatments; |
| Leukemia free survival (LFS) | up to 120 weeks | The time interval between the random date and the date of any of the following events, whichever occurs first, shall prevail: ① the date when the first bone marrow smear showed that the number of primordial cells was more than or equal to 20%; ② The first peripheral blood smear showed that the number of primordial cells was more than or equal to 20% and the absolute value of primordial cells was more than or equal to 1% × 10\^9 / L for at least 2 weeks; ③ Death from any cause; |
| Overall survival (OS) | up to 120 weeks | The time interval between the random date and death from any cause |
| The incidence and severity of adverse events (AEs) occurred during the study | up to 120 weeks | The incidence and severity of AEs occurred during the study |
| The total symptom score of MPN-SAF TSS decreased compared with baseline | up to 24 weeks | The total symptom score of MPN-SAF TSS decreased compared with baseline; |
Countries
China
Outcome results
None listed