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

Official title

An Open-Label, Positive Drug-Controlled, Parallel, Multicenter Phase II Clinical Trial of the Efficacy, Safety, and Pharmacokinetics of Flonoltinib Maleate Tablets in Patients With Intermediate to High-Risk Myelofibrosis

Overview

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)

Interventions

• Drug Flonoltinib 50mg
  Flonoltinib 50mg, QD
• Drug Flonoltinib 100mg
  Flonoltinib 100mg, QD
• 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.

Primary outcome measures

• Percentage of subjects with ≥35% reduction in spleen volume from baseline(Evaluation by IRC) [Time frame: Week 24]

Secondary outcome measures (5)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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);
• 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;
• 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;
• 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);
• Patients with a history of congenital or acquired bleeding disorders;
• Other factors that the investigator deems unsuitable for participation in the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• West China Hospital Sichuan University — Chengdu
• Hematology Hospital, Chinese Academy of Medical Sciences — Tianjin

Publications

• Yang L, Tan K, Liang R, Zhang W, Wang Y, Chen L. Assessment of flonoltinib maleate versus ruxolitinib phosphate in intermediate- to high-risk myelofibrosis (FMF-02): study protocol for a multicenter, randomized, open-label phase IIB trial. Ther Adv Hematol. 2026 Mar 19;17:20406207261424845. doi: 10.1177/20406207261424845. eCollection 2026. PMID 41883618

Identifiers

NCT: NCT06457425 · FMF-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗