Polycythemia Vera (PV)
Conditions
Keywords
PV, Gecacitinib, Pegylated Interferon, JAKi
Brief summary
The goal of this clinical trial is to evaluate the efficacy and safety of Gecacitinib in combination with pegylated interferon for the treatment of polycythemia vera (PV).The main question it aims to answer is: Can PV patients achieve hematological remission after receiving the combination therapy? Participants will: Receive combination treatment with Gecacitinib Hydrochloride Tablets and pegylated interferon for 24 weeks Visit the hospital regularly for examinations and follow-up assessments
Interventions
DRUGGecacitinib Hydrochloride Tablets；Pegylated interferon alfa-2b
Gecacitinib Hydrochloride Tablets: 100 mg twice daily (BID), orally, on an empty stomach. Pegylated interferon alfa-2b: 90 μg once weekly, subcutaneous injection in the abdomen or thigh.
Sponsors
Duan Minghui
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 years * Diagnosis of polycythemia vera (PV) according to the 2022 International Consensus Classification (ICC) criteria; * Presence of at least one of the following disease manifestations, defined as: a. Peripheral hematological abnormality: HCT ≥45% and/or PLT \>400×10⁹/L and/or WBC ≥10×10⁹/L in the absence of phlebotomy; b. Presence of weight loss \>10% over the past 6 months, night sweats, pruritus, or unexplained fever (\>37.5°C); c. Progressive splenomegaly (previous splenomegaly with an increase \>5 cm from baseline or newly developed splenomegaly); d. History of prior thrombotic or hemorrhagic events; * No current plan for stem cell transplantation; * Life expectancy \>24 weeks; * ECOG performance status 0-2; * Able to swallow tablets; * Patients without prior pegylated interferon or JAK inhibitor treatment; patients previously treated with hydroxyurea or therapeutic phlebotomy are eligible; patients who discontinued interferon for ≥6 months due to causes other than resistance or intolerance can be enrolled； * No receipt of growth factors, colony-stimulating factors, thrombopoietin, or platelet transfusion within 2 weeks prior to screening, with platelet count ≥100×10⁹/L and ANC ≥1.5×10⁹/L; * Adequate major organ function, defined asALT and AST ≤2.5 × ULN;DBIL and TBIL ≤2.0 × ULN;Serum creatinine ≤1.5 × ULN; * Peripheral blood blasts 0%; * Voluntary signed informed consent in accordance with ethics committee requirements; * Able to comply with study and follow-up procedures.
Exclusion criteria
* Any significant clinical or laboratory abnormality considered by the investigator to affect safety assessment, such as:a. Uncontrolled diabetes (\>250 mg/dL or \>13.9 mmol/L);b. Hypertension that cannot be reduced to the following range despite combination antihypertensive therapy (systolic blood pressure \<160 mmHg, diastolic blood pressure \<100 mmHg);c. Peripheral neuropathy (Grade ≥2 according to NCI-CTCAE V5.0). * History of congestive heart failure (Grade ≥3 according to NCI-CTCAE V5.0), uncontrolled or unstable angina pectoris or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 24 weeks prior to screening. * Patients who have undergone major surgery within 4 weeks prior to screening and have not fully recovered. * Patients who have received PEG-IFN-α-2a or have a history of ³²P therapy within 5 weeks prior to screening. * Patients diagnosed with primary immunodeficiency syndrome (e.g., X-linked agammaglobulinemia and common variable immunodeficiency). * Patients with arrhythmic disorders requiring treatment at screening (except digoxin). * Patients with any clinically symptomatic bacterial, viral, parasitic, or fungal infection requiring treatment at screening. * Patients with active pulmonary infection indicated by chest CT examination at screening. * Patients previously diagnosed with active tuberculosis infection, or subjects judged as suspected active tuberculosis infection by investigator at screening. * Patients who have undergone splenectomy or have received splenic radiation therapy within 48 weeks prior to screening. * Patients who are HIV positive, have active hepatitis B virus infection (HBsAg positive and HBV-DNA positive or above the normal reference range), or are anti-HCV antibody positive with HCV-RNA positive at screening. * Patients with epilepsy or those using psychiatric or sedative medications at screening (except for Estazolam tablets). * Female patients who are planning to become pregnant, are pregnant, or are breastfeeding, and patients who are unable to use effective contraception throughout the study period; male patients who do not use condoms during the administration period and for 2 days (approximately 5 half-lives) after the last dose. * Patients with a history of malignancy within the past 5 years (except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix). * Presence of other severe diseases that, in the investigator's opinion, may affect patient safety or compliance. * Patients with suspected allergy to Gecacitinib Hydrochloride, interferon, or similar drugs. * Patients with active alcohol or drug addiction that would interfere with their ability to comply with study requirements. * Patients who have participated in another investigational new drug or medical device study and have received study drug or used study device within 12 weeks prior to screening. * Patients who have used any immunomodulators, any immunosuppressants, ≥10 mg/day prednisone or equivalent corticosteroids, or are within 6 half-lives of such medications within 2 weeks prior to enrollment, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic remission rate at Week 24 | Week 24 | Simultaneous achievement of HCT \<45%, WBC \<10×10⁹/L, and PLT ≤400×10⁹/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCT remission rate | week 24 | Proportion of patients achieving HCT \<45% at 24 weeks |
| Time to HCT remission | Up to 24 weeks | Time from treatment initiation to HCT remission |
| Duration of HCT remission | Through study completion, an average of 2 year | Interval from first achievement of HCT remission to reappearance of HCT ≥45% |
| Proportion of patients achieving spleen reduction at 24 weeks | Week 4, Week 12, Week 24 | ≥10% shortening of the longest spleen diameter by palpation or normalization of spleen size |
| Proportion of patients achieving symptom improvement at 24 weeks | Week 4, Week 12, Week 24 | ≥50% reduction in total symptom score on the MPN Symptom Assessment Form. The MPN-SAF-TSS is used to assess the symptom burden of patients with myeloproliferative neoplasms. The questionnaire also reflects the quality of life of patients to a certain extent. During the diagnosis and treatment process, the MPN-10 questionnaire includes 10 sub symptoms (fatigue, early satiety, abdominal discomfort, poor activity, lack of concentration, night sweats, skin itching, bone pain, fever, and weight loss). Each item is graded from 0 (none) to 10 (heaviest), with a total score of 0-100 points. The higher the total score, the heavier the symptom burden. |
| Percentage reduction in JAK2 mutation burden after 24 weeks of treatment | Week 12, Week 24 | — |
Countries
China
Contacts
CONTACTMinghui Duan
Outcome results
None listed