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

NCT ID: NCT06457425

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-06
• Study Completion Date: 2026-07-06

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)

Conditions

MF,PMF,PPV-MF,PET-MF

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

low dose group

Flonoltinib 50mg

Group Type: EXPERIMENTAL

Flonoltinib 50mg

Intervention Type: DRUG

Flonoltinib 50mg, QD

high dose group

Flonoltinib 100mg

Group Type: EXPERIMENTAL

Flonoltinib 100mg

Intervention Type: DRUG

Flonoltinib 100mg, QD

control group

Ruxolitinib

Group Type: ACTIVE_COMPARATOR

Ruxolitinib

Intervention Type: DRUG

For patients with platelet counts between 100×10\^9/L and 200×10\^9/L, the recommended starting dose is 15 mg twice daily (bid). For patients with platelet counts \>200×10\^9/L, the recommended starting dose is 20 mg bid. For patients with platelet counts between 50×10\^9/L and \<100×10\^9/L, the recommended maximum starting dose is 5 mg bid.

Interventions

Flonoltinib 50mg

Flonoltinib 50mg, QD

Intervention Type: DRUG

Flonoltinib 100mg

Flonoltinib 100mg, QD

Intervention Type: DRUG

Ruxolitinib

For patients with platelet counts between 100×10\^9/L and 200×10\^9/L, the recommended starting dose is 15 mg twice daily (bid). For patients with platelet counts \>200×10\^9/L, the recommended starting dose is 20 mg bid. For patients with platelet counts between 50×10\^9/L and \<100×10\^9/L, the recommended maximum starting dose is 5 mg bid.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chengdu Zenitar Biomedical Technology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhijian Xiao, Doctor

Role: PRINCIPAL_INVESTIGATOR

Hematology Hospital, Chinese Academy of Medical Sciences

Ting Niu, Doctor

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital Sichuan University

Chengdu, Sichuan, China

Site Status: RECRUITING

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Liangkun Sun

Role: CONTACT

liangkunsun@zenitar.cn

15885742617

Zheng Jiang

Role: CONTACT

zhengjiang@zenitar.cn

19048075294

Facility Contacts

JingZe Zuo

Role: primary

huaxilunli@163.com

028-85422654

Qirou Wang, Doctor

Role: primary

ec@ihcams.ac.cn

022-23909095

Other Identifiers

FMF-02

Identifier Type: -

Identifier Source: org_study_id