Testing Flonoltinib for Intermediate-High Risk Myelofibrosis

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

This study is testing if flonoltinib can help people with intermediate-high risk myelofibrosis feel better and improve their health compared to another treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd (industry)
• Drugs / interventions: ruxolitinib, radiation, prednisone, flonoltinib
• Locations: 2 sites (Chengdu, Sichuan and 1 other locations)
• Trial ID: NCT06457425 on ClinicalTrials.gov

What this trial studies

This clinical trial is designed to evaluate the efficacy of flonoltinib maleate tablets in patients with intermediate-high risk myelofibrosis. Approximately 75 participants will be enrolled and assigned to one of three groups: a low-dose flonoltinib group, a high-dose flonoltinib group, or a ruxolitinib group. The trial employs a multicenter, open-label design and uses the Dynamic International Prognostic Scoring System (DIPSS) for stratification based on risk classification. The goal is to assess the treatment's impact on disease progression and patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis classified as intermediate-2 or high risk.

Not a fit: Patients with low-risk myelofibrosis or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with intermediate-high risk myelofibrosis.

How similar studies have performed: Other studies have shown promise with similar treatments for myelofibrosis, indicating potential for success in this approach.

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.

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.

Where this trial is running

Chengdu, Sichuan and 1 other locations

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

Study contacts

• Principal investigator: Zhijian Xiao, Doctor — Hematology Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Liangkun Sun

Conditions: MF,PMF,PPV-MF,PET-MF