Polycythemia Vera
Conditions
Interventions
Bezacitinib:16mg per dose, twice a day
Best Available Therapy:BAT therapy
Sponsors
The First Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 80 years old (inclusive), regardless of gender; 2. Diagnosed with PV according to the 2016 World Health Organization criteria; 3.Treatment history: having a history of resistance/intolerance to HU treatment; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 at screening; 5.Peripheral blood blast cell ratio of 0% at screening; 6.Meeting any one of the following 3 items, and Hct = 45% before randomization: Having received at least 2 times of venous phlebotomy and/or apheresis treatment within 24 weeks before screening, and b. having received at least 1 time of venous phlebotomy and/or apheresis treatment within 16 weeks before screening, and c. the farthest and nearest venous phlebotomy and/or apheresis treatments within 24 weeks before screening must be at least 4 weeks apart. Or the subject has received at least 1 time of venous phlebotomy and/or apheresis treatment within 16 weeks before screening and has an Hct > 45% at screening; Or the subject has not received venous phlebotomy and/or apheresis treatment within 24 weeks before screening, and has two consecutive measurements (with an interval of 2-14 days) of Hct > 48% at screening. 7.Blood parameters at screening must meet the following standards: ANC = 1.0 × 10?/L, platelet count (PLT) = 100 × 10?/L. 8.Basic normal function of major organs at screening, i.e., meeting the following standards: ALT and AST = 2.5 × ULN, DBIL and TBIL = 2.0 × ULN, serum creatinine = 1.5 × ULN; 9.Imaging examination (CT or MRI) showing a spleen volume = 350 cm³; 10.Voluntarily signing the informed consent form and being able to comply with the study requirements.
Exclusion criteria
Exclusion criteria: 1.Patients who have undergone major surgical procedures within the first 4 weeks of screening; 2.Patients who have received any PV-targeted treatment within 2 weeks before randomization, including hydroxyurea, recombinant interferon-a (long-acting recombinant interferon-a treatment requires 4 weeks of drug withdrawal), JAK inhibitors (such as ruxolitinib), 32P (requires 8 weeks of drug withdrawal), busulfan, etc.; 3.Patients with epilepsy or who have used psychotropic drugs or sedatives before screening (except those used for sleep aid and not affecting the safety of anxiety states); 4.Patients who have received live or attenuated vaccines within 4 weeks before screening; 5.Patients with a past or current history of any other myeloproliferative neoplasms (MPN) except PV, regardless of whether they are currently in remission; 6. Patients with grade III or above congestive heart failure (NYHA classification), unstable angina pectoris or myocardial infarction, unstable cerebrovascular accident with functional impairment, thrombotic diseases requiring anticoagulant therapy, or arrhythmic diseases requiring treatment within the first 6 months of screening; 7.Patients with a QTc interval (QTcB) > 480 ms at screening (QTcB = QT/(RR^0.5), where RR is the standardized heart rate value, obtained by dividing 60 by the heart rate); 8.Patients with active tuberculosis infection within 12 months before screening or at high risk of inducing active tuberculosis during participation in the clinical trial; 9.Patients with any clinically symptomatic bacterial, viral, parasitic, or fungal infections (except tinea unguium and Helicobacter pylori infection) requiring treatment at screening; 10.Patients with a history of malignant tumors within the past 5 years (except those with fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, breast ductal carcinoma in situ after radical surgery, thyroid cancer, and local prostate cancer); 11.Subjects with dysphagia or possible absorption disorders (including malabsorption syndrome, diseases severely affecting gastrointestinal function, inflammatory bowel disease, partial or complete intestinal obstruction, or those who have undergone gastrectomy or small bowel resection); 12.Subjects with other serious concurrent diseases that, in the investigator's opinion, may affect the patient's safety and compliance; 13.Patients with any significant clinical and laboratory abnormalities that, in the investigator's opinion, affect safety evaluation, such as: those with hypertension that cannot be controlled to the following range despite treatment with two or more antihypertensive drugs (systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg); 14. Patients who are HIV-positive at screening, or positive for active hepatitis B virus (HBsAg-positive with HBV-DNA = 1000 copies/mL or 200 IU/mL), or positive for anti-HCV antibodies with abnormal HCV-RNA; 15.Patients with suspected allergy to bonritinib or similar drugs; 16.Female patients who are planning to become pregnant, are already pregnant, or are breastfeeding, as well as patients who cannot take effective contraceptive measures throughout the trial period; 17. Patients who have participated in other clinical trials of drugs or medical devices within 4 weeks before screening or within 5 half-lives of the study drug (whichever is longer) (except for patients who failed screening).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Achieving complete hematologic remission and a reduction in spleen volume of =35% from baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in gene mutation burden relative to baseline;Symptom improvement;Duration of complete hematologic remission in those who meet the primary efficacy endpoint;The duration during which the spleen volume of those who meet the primary efficacy index is reduced by =35% compared to the baseline;The duration of treatment response in those who meet the primary efficacy endpoint;The proportion of subjects who achieved complete hematologic remission at weeks 16, 28, 40, and 52;The proportion of subjects achieving HCT control in weeks 16, 28, 40, and 52;The proportion of subjects with a spleen volume reduction of =35% at weeks 16, 28, 40, and 52;Changes in spleen volume relative to the baseline over time at weeks 16, 28, 40, and 52; | — |
Countries
China
Contacts
Public ContactJie Jin/Jian Huang
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed