Safety of Flunotinib Maleate Tablets for the Treatment of Patients With Myeloproliferative

Launched by CHENGDU ZENITAR BIOMEDICAL TECHNOLOGY CO., LTD · Nov 29, 2021

Keywords

ClinConnect Summary

The clinical trial is studying a new medication called Flonoltinib Maleate (FM) to see if it is safe and effective for treating certain blood disorders known as myeloproliferative neoplasms (MPN), which include conditions like myelofibrosis and polycythemia vera. The main goal is to check how well patients tolerate the medication and to identify the highest dose that can be safely used without causing serious side effects. Previous studies in animals have shown that FM may help reduce the size of tumors related to these conditions with fewer side effects compared to existing treatments.

To be eligible for this trial, participants need to be at least 18 years old and have a confirmed diagnosis of one of the MPNs mentioned. They should also be in a medium or high-risk category according to specific risk assessment criteria. Those who have recently undergone other cancer treatments or have certain health conditions might not be able to participate. If you join the study, you will receive FM tablets and be monitored closely for side effects and how well the medication works in your body. This trial is important because it could lead to new treatment options for people with these challenging blood disorders.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age ≥18, gender unlimited;
• • 2. Patients diagnosed as PMF, PV (PV at least 24 weeks), ET according to WHO criteria (2016 edition), or post-PV-MF or post-ET-MF according to IWG-MRT criteria;
• • 3. Any of the following criteria is met :(1) Patients receiving treatment for myeloid fibrosis must be at least medium-risk -1 or high risk as assessed according to the DIPSS risk grouping criteria; (2) PV and ET patients who are resistant or intolerant to hydroxyurea and/or interferon therapy;
• • 4. No immediate plans for a stem cell transplant;
• • 5. At least 4 weeks or more than 5 half-lives (whichever is longer) after receiving the last antitumor therapy (chemotherapy, radiotherapy, biotherapy or immunotherapy) before enrollment;
• • 6. Expected survival ≥12 weeks;
• • 7. ECOG≤2;
• • 8. Splenomegaly: palpate the margin of the spleen (the farthest point of the spleen) at least 5 cm below the costal margin; Or not accessible due to body type (obesity), but confirmed by MRI (CT scan if necessary) spleen assessment at screening time, the volume is ≥450 cm3;
• • 9. Bone marrow primitive cells and peripheral blood primitive cells ≤10%;
• • 10. PLT≥75×109 /L, ANC≥1.0×109 /μL, HGB\> without the assistance of colony stimulating factor, growth factor, thrombogenic factor or platelet infusion; 80 g/L. Subjects did not receive growth factor, colony-stimulating factor, thrombogenic factor or platelet transfusions within 2 weeks before examination.
• • 11. Heart, lung, liver, kidney, pancreas without serious organic lesions (LVEF (left ventricular ejection fraction) ≥45%; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN or CCR\> 40 ml/min. Alanine aminotransferase (ALT) ≤2×ULN; Aspartate aminotransferase (AST) ≤2×ULN;
• • 12. No severe coagulation abnormalities (PT≤1.5×ULN, APTT≤1.5×ULN, TT≤1.5×ULN);
• • 13. Those who agree to participate in the study and sign the informed consent;
• • 14. Agree to comply with the regulations of the hospital and research institution.
• Exclusion Criteria:
• • 1. The toxicity of previous anticancer therapy does not recover to grade I or below (except for hair loss), or does not fully recover from previous surgery (major surgery within 4 weeks);
• • 2. Allergic constitution, allergy to test drugs and their excipients;
• • 3. Any significant clinical or laboratory abnormalities that the investigator considers to affect the safety reviewer, such as: A. Uncontrolled diabetes - fasting glucose \> 250 mg/dL (13.9 mmol/L), b. Patients with hypertension who cannot be reduced to the following range after treatment with two or less antihypertensive drugs (systolic blood pressure \< 160 mmHg, diastolic blood pressure \< 100 mmHg), c. Peripheral neuropathy (NCI-CTC AE V5.0 Grade 2 or above);
• • 4. Patients with a history of congestive heart failure, unstable angina pectoris or myocardial infarction, cerebrovascular accidents, or pulmonary embolism within the first 6 months were screened;
• • 5. Patients with impaired heart function (Ejection fraction measured by ultrasonic electrocardiogram; ST segment descending in two or more channels in 45% or complete left bundle branch block \> 1 mm or T wave inverted; Congenital ventricular arrhythmia, clinically significant tachycardia (\>; 100 beats/min), bradycardia (lt; 50 times/min), ECG QTc \> 450 ms (male), QTc \> 480 MS (female) or clinically significant heart disease (such as unstable angina pectoris, congestive heart failure, myocardial infarction within 6 months);
• • 6. Arrhythmic disease requiring treatment, or QTC interphase (QTCB) \> 480 ms;
• • 7. Any active infections requiring treatment at the time of screening;
• • 8. Patients who had previously undergone splenectomy or who had received radiotherapy in the splenic region within 12 months prior to screening;
• • 9. Positive HIV antibody, positive active hepatitis B virus (HBsAg positive, HBV-DNA positive or ≥1000 copies/mL), positive anti-HCV antibody or HCV-RNA at screening time;
• • 10. Screening patients with epilepsy or using psychotropic drugs or sedatives;
• • 11. Pregnant or lactating women, fertile women/men who refuse to use contraceptives during the trial and within 6 months after the trial;
• • 12. Patients who have had malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years;
• • 13. Concomitant with other serious diseases that the investigator believes may affect patient safety or compliance;
• • 14. Screening patients who participated in other new drugs or medical devices and took study drugs or used study devices within the previous 1 months;
• • 15. Within 2 weeks before randomization and into the group to use any drug for MF (JAK inhibitor, hydroxyurea), any immune modulators (such as Sally degree amine), any immune inhibitors, 10 mg/day or prednisone or equivalent strength of biological effect of glucocorticoid, growth factors, such as EPO therapy, or within six drug half-life of patients;
• • 16. Intravenous use of either a potent or moderate CYP3A inhibitor (such as ketoconazole, clarithromycin, itraconazole, nefazoldone, telimycin) or a potent CYP3A4 inducer (rifampicin perforatum) within two weeks prior to initial administration;
• • 17. Patients with a history of congenital or acquired bleeding diseases;
• • 18. Alcohol dependence or drug abuse;
• • 19. People who use grapefruit, star fruit or its products within 48 hours before taking the study drug for the first time, or who do not agree to prohibit the consumption of the above-mentioned food, drink or other special diet, which may affect the absorption, distribution, metabolism and excretion of the study drug;
• • 20. Other factors considered by the investigator to be unsuitable for participation in the study.