Intermediate- to High-Risk Myelofibrosis
Conditions
Interventions
OB756:20mg per dose, twice a day
Hydroxyurea:0.5g per dose, twice a day
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 (inclusive), male or female; 2. Patients diagnosed with primary myelofibrosis (PMF) according to the WHO criteria (2016 edition) or patients diagnosed with post-polycythemia vera myelofibrosis (Post-PV-MF) or post-essential thrombocythemia myelofibrosis (Post-ET-MF) according to the IWG-MRT criteria; 3. Myelofibrosis patients assessed as intermediate-risk-2 or high-risk according to the Dynamic International Prognostic Scoring System (DIPSS) prognostic classification criteria; 4. Expected survival time greater than 24 weeks; 5. ECOG score 0 to 2; 6. Splenomegaly: the palpable splenic edge reaches or exceeds 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); 7. Peripheral blood blasts = 1.0 × 10^9/L, platelet count >= 50 × 10^9/L; 9. Within 7 days before randomization, the major organ functions are basically normal, i.e., meeting the following criteria: ALT and AST <= 2.5 × ULN; DBIL and TBIL <= 2.0 × ULN; serum creatinine <= 1.5 × ULN; 10. Voluntarily sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Patients who have previously received JAK inhibitor treatment; 2. Patients who have undergone major surgery within 4 weeks before screening; 3. Patients who have previously undergone splenectomy or received splenic radiotherapy within 3 months before screening; 4. Patients with epilepsy or those using psychotropic drugs or sedatives (except those used for hypnosis) before screening; 5. Patients who have used any treatment for MF (such as hydroxyurea, etc.) within 2 weeks before randomization, including chemotherapy, immunomodulatory therapy (e.g., thalidomide, recombinant interferon-a (long-acting recombinant interferon-a treatment requires 4 weeks of withdrawal)), androgens, immunosuppressive therapy (e.g., prednisone or corticosteroids > 10 mg/day), erythropoietin, thrombopoietin or granulocyte colony-stimulating factor, acetylsalicylic acid (aspirin) > 100 mg/day; 6. Having received blood products such as whole blood, suspended red blood cells, or platelets within 3 weeks before randomization; 7. Patients with New York Heart Association (NYHA) class III or higher congestive heart failure, unstable angina pectoris or myocardial infarction, cerebrovascular accident, thrombotic disease, or arrhythmic disease requiring treatment within 6 months before screening; 8. Patients with a QTc interval (QTcB) > 480 ms during screening; 9. Patients with active tuberculosis infection or at risk of tuberculosis infection within 12 months before screening; 10. Patients with clinically symptomatic bacterial, viral, parasitic, or fungal infections (except tinea unguium) requiring treatment during screening; 11. Having suffered from malignant tumors in the past 5 years (excluding patients with fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, radical resected breast ductal carcinoma in situ, thyroid cancer, and local prostate cancer); 12. Complicated with other serious diseases that the researcher deems may affect the patient's safety and compliance; 13. Patients with any significant clinical and laboratory abnormalities that the researcher deems to affect safety evaluation, such as: patients with hypertension that cannot be reduced to the following range after treatment with two or more antihypertensive drugs (systolic blood pressure = grade 3, according to NCI-CTCAE v5.0), etc.; 14. Positive HIV test during screening, or positive active hepatitis B virus test (HBsAg positive and HBV-DNA >= 1000 copies/mL (if the unit of HBV-DNA is IU/mL, conversion is required)), or positive anti-HCV antibody and abnormal HCV-RNA; 15. Suspected to be allergic to OB756 or similar drugs; 16. Female patients who plan to become pregnant, are already pregnant, or are breastfeeding, as well as patients who cannot take effective contraceptive measures during the entire trial period; 17. Patients who participated in other drug or medical device clinical trials within 3 months before screening (excluding patients who failed screening).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects with a reduced spleen volume of =35% at 24 weeks accounted for all subjects(IRC Evaluation); | — |
Secondary
| Measure | Time frame |
|---|---|
| Spleen Response: Defined as the proportion of patients achieving >=35% reduction in spleen volume from baseline on at least one assessment.;The proportion of subjects with a reduced spleen volume of >=35% at 24 weeks accounted for all subjects(researcher Evaluation);The proportion of subjects with a reduced spleen volume of >=35% at 12 weeks accounted for all subjects(IRC&researcher Evaluation);Occurrence of adverse events;Plasma Concentration;Spleen Response: Defined as the proportion of patients achieving >=35% reduction in spleen volume from baseline on at least one assessment.;The change in JAK2 gene mutation burden compared to the baseline;Objective Response Rate (ORR);Improvement in MF-Related Symptoms;Progression-Free Survival (PFS);LFS;OS:; | — |
Countries
China
Contacts
Public ContactJie Jin
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed