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Myeloproliferative Neoplasm (MPN)Phase 1/2NCT05153343

Safety of Flonoltinib Maleate Tablets for the Treatment of Patients With Myeloproliferative

A Phase 1/2 study testing flonoltinib 25mg, flonoltinib 100mg and flonoltinib 150mg in people with Myeloproliferative Neoplasm (MPN) and Myelofibrosis，MF, run by Chengdu Zenitar Biomedical Technology Co., Ltd at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Flonoltinib Maleate (FM) targets Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). FM is a dual target inhibitor of JAK2/FLT3.FM has the activity of inhibiting JAK2 signaling pathway, and pharmacodynamics evaluation also confirmed that FM has a good therapeutic effect on the primary splenomegaly model of… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
flonoltinib 25mg, flonoltinib 100mg and flonoltinib 150mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteChina
Study dates
27 Dec 2021to 19 Mar 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18, gender unlimited;
  • Patients diagnosed as PMF, PV (PV at least 24 weeks), ET according to WHO criteria (2016 edition), or post-PV-MF or post-ET-MF according to IWG-MRT criteria;
  • Any of the following criteria is met :(1) Patients receiving treatment for myeloid fibrosis must be at least medium-risk -1 or high risk as assessed according to the DIPSS risk grouping criteria; (2) PV and ET patients who are resistant or intolerant to hydroxyurea and/or interferon therapy;
  • No immediate plans for a stem cell transplant;
  • At least 4 weeks or more than 5 half-lives (whichever is longer) after receiving the last antitumor therapy (chemotherapy, radiotherapy, biotherapy or immunotherapy) before enrollment;
  • Expected survival ≥12 weeks;
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  • ECOG≤2;
  • Splenomegaly: palpate the margin of the spleen (the farthest point of the spleen) at least 5 cm below the costal margin; Or not accessible due to body type (obesity), but confirmed by MRI (CT scan if necessary) spleen assessment at screening time, the volume is ≥450 cm3;
  • Bone marrow primitive cells and peripheral blood primitive cells ≤10%;
  • PLT≥75×109 /L, ANC≥1.0×109 /μL, HGB> without the assistance of colony stimulating factor, growth factor, thrombogenic factor or platelet infusion; 80 g/L. Subjects did not receive growth factor, colony-stimulating factor, thrombogenic factor or platelet transfusions within 2 weeks before examination.
  • Heart, lung, liver, kidney, pancreas without serious organic lesions (LVEF (left ventricular ejection fraction) ≥45%; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN or CCR> 40 ml/min. Alanine aminotransferase (ALT) ≤2×ULN; Aspartate aminotransferase (AST) ≤2×ULN;
  • No severe coagulation abnormalities (PT≤1.5×ULN, APTT≤1.5×ULN, TT≤1.5×ULN);
  • Those who agree to participate in the study and sign the informed consent;
  • Agree to comply with the regulations of the hospital and research institution.

Who cannot join

  • The toxicity of previous anticancer therapy does not recover to grade I or below (except for hair loss), or does not fully recover from previous surgery (major surgery within 4 weeks);
  • Allergic constitution, allergy to test drugs and their excipients;
  • Any significant clinical or laboratory abnormalities that the investigator considers to affect the safety reviewer, such as: A. Uncontrolled diabetes - fasting glucose > 250 mg/dL (13.9 mmol/L), b. Patients with hypertension who cannot be reduced to the following range after treatment with two or less antihypertensive drugs (systolic blood pressure < 160 mmHg, diastolic blood pressure < 100 mmHg), c. Peripheral neuropathy (NCI-CTC AE V5.0 Grade 2 or above);
  • Patients with a history of congestive heart failure, unstable angina pectoris or myocardial infarction, cerebrovascular accidents, or pulmonary embolism within the first 6 months were screened;
  • Patients with impaired heart function (Ejection fraction measured by ultrasonic electrocardiogram; ST segment descending in two or more channels in 45% or complete left bundle branch block > 1 mm or T wave inverted; Congenital ventricular arrhythmia, clinically significant tachycardia (>; 100 beats/min), bradycardia (lt; 50 times/min), ECG QTc > 450 ms (male), QTc > 480 MS (female) or clinically significant heart disease (such as unstable angina pectoris, congestive heart failure, myocardial infarction within 6 months);
  • Arrhythmic disease requiring treatment, or QTC interphase (QTCB) > 480 ms;
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  • Any active infections requiring treatment at the time of screening;
  • Patients who had previously undergone splenectomy or who had received radiotherapy in the splenic region within 12 months prior to screening;
  • Positive HIV antibody, positive active hepatitis B virus (HBsAg positive, HBV-DNA positive or ≥1000 copies/mL), positive anti-HCV antibody or HCV-RNA at screening time;
  • Screening patients with epilepsy or using psychotropic drugs or sedatives;
  • Pregnant or lactating women, fertile women/men who refuse to use contraceptives during the trial and within 6 months after the trial;
  • Patients who have had malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years;
  • Concomitant with other serious diseases that the investigator believes may affect patient safety or compliance;
  • Screening patients who participated in other new drugs or medical devices and took study drugs or used study devices within the previous 1 months;
  • Within 2 weeks before randomization and into the group to use any drug for MF (JAK inhibitor, hydroxyurea), any immune modulators (such as Sally degree amine), any immune inhibitors, 10 mg/day or prednisone or equivalent strength of biological effect of glucocorticoid, growth factors, such as EPO therapy, or within six drug half-life of patients;
  • Intravenous use of either a potent or moderate CYP3A inhibitor (such as ketoconazole, clarithromycin, itraconazole, nefazoldone, telimycin) or a potent CYP3A4 inducer (rifampicin perforatum) within two weeks prior to initial administration;
  • Patients with a history of congenital or acquired bleeding diseases;
  • Alcohol dependence or drug abuse;
  • People who use grapefruit, star fruit or its products within 48 hours before taking the study drug for the first time, or who do not agree to prohibit the consumption of the above-mentioned food, drink or other special diet, which may affect the absorption, distribution, metabolism and excretion of the study drug;
  • Other factors considered by the investigator to be unsuitable for participation in the study.

Trial locations and contacts

1 site in 1 country.

China1 site

  • West China Hospital Sichuan University

    Chengdu, Sichuan, 610000

Other trials in China

About this study

Official title: Safety of Flonoltinib Maleate Tablets for the Treatment of Patients With Myeloproliferative Neoplasms Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of the Phase I/II Trial

Flonoltinib Maleate (FM) targets Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). FM is a dual target inhibitor of JAK2/FLT3.FM has the activity of inhibiting JAK2 signaling pathway, and pharmacodynamics evaluation also confirmed that FM has a good therapeutic effect on the primary splenomegaly model of mice induced by JAK2V617 mutation.Therefore, FM has the potential to treat bone marrow proliferative tumors.The drug is intended to be used in patients with MPN, mainly including medium-risk or high-risk myelofibrosis (FM) (including primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PostPV-MF) and post-primary thrombocythemia myelofibrosis (postET-MF)), Polycythemia vera (PV) and essential thrombocythemia (ET) were the primary causes of thrombocythemia and thrombocythemia.

FM has high inhibitory activity against JAK family and FLT3 kinase, suggesting that FM may have a certain therapeutic effect on AML disease.

Read more

In vitro experiments on the proliferation of JAK2-dependent and Flt3-related tumor cell lines with FM showed that the tumor cell lines had a significant inhibitory effect. The IC50 of half of the tumor cell lines was less than 0.5 μm, which was better than or equal to the similar drugs Ruxolitinib and Fedratinib.

The effect of FM on tumor cells from MPN patients indicated that FM has the potential to treat MPN disease.

In multiple animal models of bone marrow proliferative tumors with JAK2V617F mutations, FM showed superior efficacy and low toxicity (no obvious VISCAL toxicity) than existing drugs on the market, and the tumor inhibition effect of FM showed a good dose-dependent relationship.

Objectives of Study

Main Purpose:

  1. Tolerance and safety of flonoltinib maleate Tablets tablets in patients with bone marrow proliferative tumors;
  2. To observe the possible dose-limiting toxicity(DLT) of flonoltinib maleate tablets in patients with bone marrow proliferative tumors,To determine the maximum tolerated dose(MTD) of flonoltinib maleate tablets,To provide the basis for the recommended dose and design scheme of the later clinical trial.

Secondary Purpose:

  1. To evaluate the pharmacokinetic characteristics of single and repeated oral administration of flonoltinib maleate tablets in patients with bone marrow proliferative tumors;
  2. To evaluate the primary efficacy of single and multiple oral flonoltinib maleate tablets in patients with bone marrow proliferative tumors.
Being tested
flonoltinib 25mg, flonoltinib 100mg, flonoltinib 150mg, flonoltinib 225mg, flonoltinib 50mg
Medical subject headings
Myeloproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • flonoltinib 25mgDrug

    1 case,The starting dose.Take the medicine once on Day1and Day 5-21，and then 14 days per cycle.

  • flonoltinib 100mgDrug

    Take the medicine once on Day1and Day 5-21，and then 14 days per cycle.

  • flonoltinib 150mgDrug

    Take the medicine once on Day1and Day 5-21，and then 14 days per cycle.

  • flonoltinib 225mgDrug

    Take the medicine once on Day1and Day 5-21，and then 14 days per cycle.

  • flonoltinib 50mgDrug

    Take the medicine once on Day1and Day 5-21，and then 14 days per cycle.

Study groups in NCT05153343
Study groupRoleWhat they receive
Dose escalation group 1ExperimentalFlonoltinib 25mg
Receives: Drug: flonoltinib 25mg
Dose escalation group 2ExperimentalFlonoltinib 50mg
Receives: Drug: flonoltinib 50mg
Dose escalation group 3ExperimentalFlonoltinib 100mg
Receives: Drug: flonoltinib 100mg
Dose escalation group 4ExperimentalFlonoltinib 150mg
Receives: Drug: flonoltinib 150mg
Dose exploration stage group 5ExperimentalFlonoltinib 225mg
Receives: Drug: flonoltinib 225mg
Extended Phase Dose GroupExperimentalFlonoltinib 100mg
Receives: Drug: flonoltinib 100mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Flonoltinib Maleate Pharmacokinetics (PK)：Cmax

    Estimation of maximum observed plasma concentration

    Measured: 72hours

  2. Flonoltinib Maleate Pharmacokinetics (PK)：Tmax

    Estimation of time to reach Cmax

    Measured: 72hours

  3. Flonoltinib Maleate Pharmacokinetics (PK)：AUC0-72h

    Estimation of AUC from time zero to the last measured time point

    Measured: 72hours

  4. Flonoltinib Maleate Pharmacokinetics (PK)：AUC0-∞

    Estimation of AUC from time zero extrapolated to infinity

    Measured: 72hours

  5. Flonoltinib Maleate Pharmacokinetics (PK)：MRT

    Estimation of mean residence time

    Measured: 72hours

  6. Flonoltinib Maleate Pharmacokinetics (PK)：Vd

    Estimation of apparent volume of distribution

    Measured: 72hours

  7. Flonoltinib Maleate Pharmacokinetics (PK)：t1/2

    Estimation of terminal elimination half-life

    Measured: 72hours

  8. Flonoltinib Maleate Pharmacokinetics (PK)：CLz/F

    Estimation of clearance when dosed orally

    Measured: 72hours

  9. Flonoltinib Maleate Pharmacokinetics (PK)：Vz/F

    Estimation of apparent volume of distribution when dosed orally

    Measured: 72hours

  10. Flonoltinib Maleate Pharmacokinetics (PK)：Ke

    Estimation of the elimination rate constant of a drug in the body

    Measured: 72hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2021
  2. Study start27 Dec 2021
  3. Primary completion29 Nov 2023
  4. Study completion19 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05153343
Sponsor's protocol ID
FMF-01
Status last verified
Sep 2025
First submitted
29 Nov 2021
Last updated
1 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing flonoltinib 25mg, flonoltinib 100mg and flonoltinib 150mg in people with Myeloproliferative Neoplasm (MPN) and Myelofibrosis，MF, run by Chengdu Zenitar Biomedical Technology Co., Ltd at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Flonoltinib Maleate Pharmacokinetics (PK)：Cmax (time frame: 72hours). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05153343.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.

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