A Phase II Clinical Trial of Flonoltinib Maleate Tablet in Intermediate-High Risk Myelofibrosis

Phase 2

Recruiting

• Conditions: MF,PMF,PPV-MF,PET-MF
• Interventions: Drug: Flonoltinib 50mg; Drug: Flonoltinib 100mg; Drug: Ruxolitinib

• Registration Number: NCT06457425
• Lead Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

Brief Summary

This trial adopts a multicenter, open-label, positive drug parallel control clinical trial design, planning to enroll approximately 75 MF participants. Eligible participants will be stratified and assigned in a 1:1:1 ratio to the low-dose flonoltinib maleate tablet group, high-dose flonoltinib maleate tablet group, or the ruxolitinib tablet group. Stratification factor include the Dynamic International Prognostic Scoring System (DIPSS) risk classification (intermediate-2 and high risk)

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-06
• Study First Submitted: 2024-06-07
• Study First Submitted QC: 2024-06-07
• Study First Posted: 2024-06-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-10
• Primary Completion: 2026-05-06
• Study Completion: 2026-07-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Age ≥ 18 years, no gender restrictions;
2. Diagnosed with primary myelofibrosis (PMF) according to WHO criteria (2016 edition) or post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) according to IWG-MRT criteria;
3. Evaluated as intermediate-2 or high-risk myelofibrosis according to the Dynamic International Prognostic Scoring System (DIPSS) risk classification;
4. Expected survival ≥ 24 weeks;
5. ECOG score of 0-2;
6. Splenomegaly: palpable spleen edge reaching or exceeding 5 cm below the costal margin (distance from the intersection of the left midclavicular line and the left costal margin to the farthest point of the spleen); or not palpable due to body habitus (obesity) but confirmed by magnetic resonance imaging (MRI ) (or CT scan if necessary) at screening with spleen volume ≥ 450 cm³;
7. Blasts in peripheral blood and bone marrow ≤ 10%; 8) Within 7 days before the first dose, absolute absolute neutrophil count (ANC )≥ 1.0×10^9/L, platelet count ≥ 50×10^9/L, hemoglobin (HGB )> 60 g/L (participants should not have received growth factors, colony-stimulating factors, thrombopoietic agents, or platelet transfusions within 2 weeks before the baseline assessment prior to the first dose); 9) Major organ function basically normal within 7 days before the first dose; 10) Able to understand and voluntarily sign the informed consent form.

Exclusion Criteria

1. Previous anticancer treatment-related toxic reactions have not recovered to grade 1 or below (excluding alopecia and conditions specified in inclusion criteria 8 and 9), or have not fully recovered from previous surgery (major surgery within 4 weeks);
2. Hypersensitivity, allergic to the investigational drug or its excipients;
3. Previous intolerance or resistance to ruxolitinib;
4. Use of JAK inhibitors within 4 weeks before the first dose;
5. Any significant clinical and laboratory abnormalities that, in the investigator's opinion, affect safety evaluation;
6. History of congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident (excluding lacunar infarction), or pulmonary embolism within 6 months prior to screening;
7. Impaired cardiac function or arrhythmic disease requiring treatment at screening;
8. Any active infection requiring intravenous antibiotic treatment at screening;
9. Active tuberculosis infection within 48 weeks prior to screening or latent tuberculosis infection indicated by tuberculosis-related tests during the screening period;
10. Patients who have undergone splenectomy or received radiation therapy to the spleen area within 12 months before the first dose;
11. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, except for: a) HBV infection: Patients with positive hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) with undetectable peripheral blood HBV-DNA (below the detection limit of the testing laboratory) can be enrolled; they must continue antiviral therapy and have HBV-DNA testing every 12 weeks and at the end of treatment (EOT); b) HCV seropositive patients with negative HCV RNA can be enrolled.
12. Positive for human immunodeficiency virus antibody (HIV-Ab) or Treponema pallidum antibody (TP-Ab) (patients with positive Treponema pallidum antibody can have a titer test, and the investigator will determine eligibility based on comprehensive judgment);
13. Patients with epilepsy or those using psychiatric drugs or sedatives at screening (excluding those used for sleep purposes);
14. Pregnant or breastfeeding women, and patients with reproductive potential (male and female) who refuse to use contraceptive measures during the trial and for 6 months after the trial;
15. Patients who have had another malignancy within 5 years before the first dose (excluding cured in-situ carcinoma and basal cell carcinoma of the skin);
16. Patients with other severe diseases that, in the investigator's opinion, may affect safety or compliance;
17. Patients who participated in other clinical trials of investigational drugs or medical devices within 1 month before the first dose and used the investigational drug or device;
18. Use of any treatment for MF (other than JAK inhibitors) within 2 weeks or 5 half-lives (whichever is longer) before the first dose, any immunomodulatory agents (e.g., thalidomide), any immunosuppressants, ≥10 mg/day prednisone or equivalent biological potency corticosteroids, or growth factors (e.g., erythropoietin (EPO)) (Traditional Chinese medicine should be stopped 1 day before the first dose);
19. Patients with a history of congenital or acquired bleeding disorders;
20. Other factors that the investigator deems unsuitable for participation in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
low dose group	Flonoltinib 50mg	Flonoltinib 50mg
high dose group	Flonoltinib 100mg	Flonoltinib 100mg
control group	Ruxolitinib	Ruxolitinib

Primary Outcome Measures

Name	Time	Method
Percentage of subjects with ≥35% reduction in spleen volume from baseline(Evaluation by IRC)	Week 24	Percentage of subjects with ≥35% reduction in spleen volume from baseline(Evaluation by IRC)

Secondary Outcome Measures

Name	Time	Method
Percentage of subjects with ≥35% reduction in spleen volume from baseline (Evaluation by researcher)	Week 12	Percentage of subjects with ≥35% reduction in spleen volume from baseline (Evaluation by researcher)
Percentage of subjects with ≥35% reduction in spleen volume from baseline (Evaluation by IRC)	Week 12	Percentage of subjects with ≥35% reduction in spleen volume from baseline( Evaluation by IRC)
Percentage of subjects with ≥50% reduction in MPN-SAF TSS scale total symptom score	Week 24 and Week 12	Percentage of subjects with ≥50% reduction in MPN-SAF TSS scale total symptom score
Objective response rate (ORR = CR + PR) per the IWG-MRT consensus criteria.	Week 24	Objective response rate (ORR = CR + PR) per the IWG-MRT consensus criteria.

Trial Locations

Locations (2)

West China Hospital Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Hematology Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China