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

NCT06457425 | Recruiting Phase 2

• 1 other identifier: FMF-02
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects with ≥35% reduction in spleen volume from baseline(Evaluation by IRC)

  Percentage of subjects with ≥35% reduction in spleen volume from baseline(Evaluation by IRC)

  Week 24

Secondary Outcomes (5)

• Percentage of subjects with ≥35% reduction in spleen volume from baseline (Evaluation by researcher)

  Week 24

• 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 IRC)

  Week 12

• Percentage of subjects with ≥50% reduction in MPN-SAF TSS scale total symptom score

  Week 24 and Week 12

• Objective response rate (ORR = CR + PR) per the IWG-MRT consensus criteria.

  Week 24

Study Arms (3)

low dose group

EXPERIMENTAL

Flonoltinib 50mg

Drug: Flonoltinib 50mg

high dose group

EXPERIMENTAL

Flonoltinib 100mg

Drug: Flonoltinib 100mg

control group

ACTIVE COMPARATOR

Ruxolitinib

Drug: Ruxolitinib

Interventions

Flonoltinib 50mg DRUG

Flonoltinib 50mg, QD

low dose group

Flonoltinib 100mg DRUG

Flonoltinib 100mg, QD

high dose group

Ruxolitinib 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.

control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, no gender restrictions;
• 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;
• Evaluated as intermediate-2 or high-risk myelofibrosis according to the Dynamic International Prognostic Scoring System (DIPSS) risk classification;
• Expected survival ≥ 24 weeks;
• ECOG score of 0-2;
• 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;
• 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.

You may not qualify if:

• Hypersensitivity, allergic to the investigational drug or its excipients;
• Previous intolerance or resistance to ruxolitinib;
• Use of JAK inhibitors within 4 weeks before the first dose;
• Any significant clinical and laboratory abnormalities that, in the investigator's opinion, affect safety evaluation;
• History of congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident (excluding lacunar infarction), or pulmonary embolism within 6 months prior to screening;
• Impaired cardiac function or arrhythmic disease requiring treatment at screening;
• Any active infection requiring intravenous antibiotic treatment at screening;
• Active tuberculosis infection within 48 weeks prior to screening or latent tuberculosis infection indicated by tuberculosis-related tests during the screening period;
• Patients who have undergone splenectomy or received radiation therapy to the spleen area within 12 months before the first dose;
• 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.
• 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);
• Patients with epilepsy or those using psychiatric drugs or sedatives at screening (excluding those used for sleep purposes);
• 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;
• 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);
• Patients with other severe diseases that, in the investigator's opinion, may affect safety or compliance;

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (2)

West China Hospital Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300052, China

RECRUITING

MeSH Terms

Interventions

ruxolitinib

Study Officials

• Zhijian Xiao, Doctor

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Ting Niu, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liangkun Sun

CONTACT

15885742617; liangkunsun@zenitar.cn

Zheng Jiang

CONTACT

19048075294; zhengjiang@zenitar.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 13, 2024
• Study Start: May 6, 2024
• Primary Completion: May 6, 2026
• Study Completion (Estimated): July 6, 2026
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

CN (2)