Flonoltinib maleate treatment for intermediate- or high-risk myelofibrosis

A Randomized, Open-label, Positive-controlled, Parallel-grouped, Multicenter Phase III Clinical Trial on the Efficacy and Safety of Flonoltinib Maleate Tablets in Patients With Intermediate- or High-risk Myelofibrosis

This trial will test flonoltinib versus ruxolitinib in adults 18–80 with intermediate- or high-risk myelofibrosis and enlarged spleens to see if flonoltinib better reduces spleen size and symptoms.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 105 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd (Industry-sponsored)
• Locations: 2 sites (Chengdu, Sichuan and 1 other locations)
• Trial ID: NCT07317700 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label Phase 3 trial enrolling about 105 participants with primary or post‑polycythemia vera/post‑essential thrombocythemia myelofibrosis. Participants are randomized 2:1 to receive flonoltinib 75 mg or ruxolitinib, with randomization stratified by DIPSS prognostic grade. Treatment is taken continuously until pre-specified withdrawal criteria are met, and outcomes such as spleen size and symptom control will be monitored over the treatment period. The trial is conducted at tertiary hematology centers in China and uses standard eligibility requirements including ECOG 0–2 and adequate organ function.

Who should consider this trial

Good fit: Adults aged 18–80 with primary MF or post‑PV/post‑ET MF, ECOG 0–2, expected survival >24 weeks, palpable splenomegaly ≥5 cm (or spleen volume ≥450 cm³ by imaging) and adequate liver and kidney function are the intended participants.

Not a fit: Patients with low‑risk disease, poor performance status (ECOG >2), significant organ dysfunction, or very short expected survival are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, flonoltinib could provide an additional oral treatment option that reduces spleen size and symptoms for patients with intermediate- or high-risk myelofibrosis, potentially improving quality of life.

How similar studies have performed: Other JAK inhibitor programs such as ruxolitinib and fedratinib have demonstrated meaningful reductions in spleen size and symptom burden, while flonoltinib represents a novel agent being directly compared to standard therapy.

Eligibility criteria

Inclusion Criteria:

1. Age range of 18-80 years old (including threshold), gender not limited;
2. Patients diagnosed with primary myelofibrosis (PMF) according to WHO criteria (2016 edition) or patients diagnosed with post polycythemia vera myelofibrosis (PPV-MF) or post thrombocytopenia myelofibrosis (PET-MF) according to IWG-MRT criteria;
3. Expected survival period greater than 24 weeks;
4. ECOG score 0-2 points;
5. Splenomegaly: Palpation of the splenic margin reaching or exceeding 5cm below the rib (distance from the intersection of the left clavicle midline and left rib margin to the farthest point of the spleen); Or due to physical reasons (such as obesity), it may not be palpable, but MRI/CT spleen evaluation during screening confirms a volume of \>= 450 cm\^3;
6. Within 7 days prior to randomization, the main organ functions were generally normal, meeting the following criteria: ALT and AST \<= 2.5 × ULN; TBIL\<=2.0×ULN； Serum creatinine \<=1.5 × ULN or serum creatinine clearance rate (Ccr)\>50 mL/min; INR, PT, and APTT \<= 1.5 × ULN;
7. Can understand and voluntarily sign an informed consent form.

Exclusion Criteria:

1. The toxic reactions of previous anti-cancer treatments have not recovered to grade 1 or below (excluding hair loss), or have not fully recovered from previous surgeries;
2. Allergy to experimental drugs and their excipients;
3. For any significant clinical and laboratory abnormalities, the researchers believe that they affect the safety evaluators, such as: a. uncontrollable diabetes - fasting blood glucose\>250 mg/dL (13.9 mmol/L), b. hypertension and cannot be reduced to the following range after treatment with two or more antihypertensive drugs (systolic blood pressure\<160 mmHg, diastolic blood pressure\<100 mmHg), c. peripheral neuropathy;
4. Patients with a history of congestive heart failure (NYHA grade III or above), unstable angina or myocardial infarction, cerebrovascular accidents or thromboembolism within the first 6 months of screening;
5. Individuals with impaired cardiac function (those with ejection fraction\<45% detected by echocardiography, congenital ventricular arrhythmia, QTcF\>450 ms on electrocardiogram (males), QTcF\>470 ms on electrocardiogram (females), or those with arrhythmia requiring treatment at the time of screening);
6. Patients with congenital or acquired bleeding disorders or unstable thrombotic diseases requiring anticoagulant therapy;
7. Any active infection requiring systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) within the first 14 days of randomization;
8. Active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: a) HBV infection: patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and undergo peripheral blood HBV-DNA testing, with the lower limit of HBV-DNA detection value (i.e. the upper limit of normal value in the laboratory of each research center) can be enrolled; If the baseline HBsAg is positive, continuous antiviral treatment is required after enrollment, and HBV-DNA testing should be conducted every 12 weeks and at EOT visits; b) Patients who are positive for HCV serology but negative for HCV-RNA can be included in the study;
9. Patients who are positive for human immunodeficiency virus antibodies (HIV Ab) or anti Treponema pallidum antibodies (TP Ab) (Treponema pallidum antibodies positive);
10. Patients with epilepsy or those taking psychotropic or sedative drugs during screening;
11. Pregnant or lactating female patients, female/male patients with fertility who refuse to use contraceptive measures during the trial period and within 6 months after the trial ends;
12. Patients who have suffered from other malignant tumors within the past 5 years before the first administration (excluding cured carcinoma in situ and basal cell carcinoma of the skin);
13. Patients with combined swallowing difficulties;
14. Patients who participated in clinical trials of other new drugs or medical devices within the first month of randomization and took the study drug or used the study device;
15. Researchers believe that there are other factors that are not suitable for participating in the experiment.

Where this trial is running

Chengdu, Sichuan and 1 other locations

• West China Hospital Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS) — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xiao Zhijian, Doctor — Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS)
• Study coordinator: Wang Fangmei

Conditions MF