Polycythemia Vera
Conditions
Interventions
Dose exploration stage group 1:Flonoltinib Maleate Tablet 75mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Dose exploration stage group 2:Flonoltinib Maleate Tablet 100mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Dose exploration stage group 3:Flonoltinib Maleate Tablet 125mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Extended Phase Dose Group 1:Flonoltinib Maleate Tablet, oral administration, once daily, given on an empty stomach.
Extended Phase Dose Group 2:Flonoltinib Maleate Tablet, oral administration, once daily, given on an empty stomach.
Extended Phase Dose Group 3:Flonoltinib Maleate Tablet, oral administration, once daily, given on an empty stomach.
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS);West China Hospital of Sichuan University;Shengjing Hospital Of China Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years old and gender not limited when signing the informed consent form; 2. Diagnosed as PV according to WHO standards (2016 edition), and resistant/intolerant to hydroxyurea or interferon treatment (refer to attachments 1 and 2); 3. When screening, the peripheral blood primitive cells are 0%; 4. Meet any of the following criteria and achieve HCT 45% at the time of screening; (3) Has not undergone venous bloodletting and/or apheresis treatment within the 24 weeks prior to screening, and has had HCT > 48% measured twice in a row (with an interval of 2–14 days) during screening; 5. When screening, laboratory test indicators meet the following criteria: neutrophil count >= 1.0 × 10^9/L, platelet count >= 100 × 10^9/L and <= 1000 × 10^9/L; ALT and AST <= 2.5 × ULN; TBIL <= 2.0 × ULN; serum creatinine <= 1.5 × ULN; 6. When screening, the Eastern Cooperative Oncology Group (ECOG) performance status score is 0–2; 7. Can understand and voluntarily sign an informed consent form.
Exclusion criteria
Exclusion criteria: 1. Individuals with allergies or suspected allergies to the test drug and its excipients; 2. The toxic reactions of previous anti-cancer treatments have not recovered to grade 1 or below (excluding hair loss; blood routine and blood biochemical indicators refer to inclusion criteria 4 and 5), or have not fully recovered from previous surgeries (having undergone major surgery within 4 weeks); 3. In addition to PV, any other myeloproliferative neoplasms (MPN), including post-polycythemia vera myelofibrosis (PPV-MF) (myelofibrosis grading in accordance with MF-2 or MF-3), may also be present; 4. Any active infections that require systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) during screening; 5. Patients with swallowing difficulties, chronic diarrhea, or oral absorption disorders identified during screening; 6. Patients with underlying diseases difficult to control with medication during screening, including but not limited to: diabetes (fasting blood glucose > 250 mg/dL or 13.9 mmol/L), hypertension (systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg), peripheral neuropathy (NCI-CTC AE v5.0 grade 2 or above); 7. Individuals who have experienced congestive heart failure (NYHA class III or above), unstable angina, myocardial infarction, cerebrovascular accidents with functional impairment, or require treatment for arrhythmia within the past 6 months; 8. Individuals with QTcF > 450 ms (male) or QTcF > 470 ms (female) on electrocardiogram during screening; 9. Individuals who have experienced active tuberculosis infection within the past year prior to screening, or those whose tuberculosis-related test results indicate latent infection during screening (excluding those who have completed a full course of preventive anti-tuberculosis treatment; see Annex 6 for details); 10. Patients who have undergone splenectomy or splenic radiotherapy in the past (excluding those with persistent increase in splenic volume after radiotherapy); 11. During screening, any of the following conditions exist: (1) Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) is positive, and HBV-DNA detection is positive or above the upper limit of normal; (2) HCV antibody positive and HCV-RNA detection positive; (3) Positive for anti-Treponema pallidum antibody (TP-Ab) and positive for Treponema pallidum non-specific antibody (PRP or TRUST) detection; (4) Positive for Human Immunodeficiency Virus Antibody (HIV-Ab); 12. Individuals with epilepsy or mental illnesses requiring medication during screening (excluding insomnia); 13. Individuals who have been diagnosed with other malignant tumors within the past 5 years prior to first dosing (excluding cured carcinoma in situ and basal cell carcinoma of the skin); 14. Patients with congenital or acquired bleeding disorders or active thrombotic disorders during screening (excluding those who have received stable anticoagulant therapy for more than 3 months with no new thrombosis); 15. Presence of other serious diseases during screening that, in the investigator’s judgment, may affect patient safety or compliance; 16. Use of any PV therapeutic drugs within 2 weeks prior to trial administration or within 5 half-lives (whichever is longer), including hydroxyurea, recombinant interferon-a (long-acting recombinant interferon-a requires discontinuation for 4 weeks), JAK inhibitors (e.g., ruxolitinib), ³²P (require
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| At the end of the 28th week of treatment, the proportion of subjects who achieved HCT control (HCT control is defined as achieving HCT<45% without undergoing venous bloodletting or apheresis treatment); | — |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of subjects who achieved HCT control at each time point at the end of treatment in weeks 16, 40, and 52;The proportion of subjects who achieved complete hematological remission at the end of weeks 28 and 52 of treatment (complete hematological remission is defined as HCT= 45%);Changes in HCT, WBC, and PLT over time relative to baseline at the end of treatment in weeks 16, 28, 40, and 52;Changes in the total symptom score of MPN-SAF TSS scale at each time point compared to baseline at the end of treatment in weeks 16, 28, 40, and 52;The proportion of subjects whose total symptom score on the MPN-SAF TSS scale decreased by 50% from baseline at the end of treatment at weeks 16, 28, 40, and 52;Changes in itch scores of MPN-SAF TSS scale compared to baseline at the end of treatment in weeks 16, 28, 40, and 52;Changes in EORTC-QLQ C30 Scale Scores from Baseline at the End of Treatment Weeks 16, 28, 40, and 52;Proportion of subjects who did not experience thrombosis or bleeding events at the end of treatment in weeks 28 and 52;Changes in gene mutation burden relative to baseline at the end of treatment in weeks 28 and 52; | — |
Countries
China
Contacts
Public ContactLei Zhang;Ting Niu/Jia Miao;Wei Yang
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (IHCAMS);West China Hospital of Sichuan University;Shengjing Hospital Of China Medical University
Outcome results
None listed