Myeloproliferative tumor
Conditions
Interventions
test group:Oral XH-5102 tablets
Sponsors
Shanghai Sixth People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1) Age = 18 years old, male or female; 2) According to the PMF, PV and ET standards issued by the World Health Organization (WHO) in 2016 and the PPV-MF and PET-MF standards recommended by the International Working Group on Bone Marrow Fibrosis Research and Treatment (IWG-MRT), the diagnosis of patients must be PMF, PV, ET, PPV-MF or PET-MF (regardless of the mutation status of JAK2); 3) The following conditions of the dose-increasing study meet any one of the following: (1) According to the Dynamic International Prognosis Score System (DIPSS), patients with bone marrow fibrosis who must be at least at medium risk - 1 or above and who have received treatment (with one or more factors that affect the prognosis), are fully satisfied with the previous treatment or intolerance of Lucotinib, and the relevant acceptable definitions are as follows: Lucotinib is refractory: Lucotinib treatment = 3 months, Magnetic resonance imaging (MRI) showed that the spleen volume decreased by less than 10%, or palpation showed that the spleen volume decreased by less than 30% from the baseline, or regrowth (recurrence) after initial response. Lucotinib intolerance: Lucotinib treatment = 28 days complicated with any of the following symptoms (intolerance): the need for blood transfusion of red blood cells (at least 2 units/month, and lasting for 2 months) or = grade 3 adverse reactions when receiving Lucotinib treatment, such as thrombocytopenia, anemia, hematoma and/or bleeding. (2) For primary thrombocytosis (ET), hydroxyurea and/or interferon are resistant or intolerant and have received second-line treatment. (3) For polycythemia vera (PV), hydroxyurea and/or interferon are resistant or intolerant and have received second-line treatment. Definition of hydroxyurea resistance or intolerance in PV: 1 After 3 months of treatment with hydroxyurea, blood still needs to be bled to maintain hematocrit400 × 109/LWBC>10x109/L) 3 After 3 months of treatment with hydroxyurea, the palpated giant spleen failed to shrink by more than 50% or the clinical symptoms related to splenomegaly failed to completely relieve 4 Under the minimum dose of hydroxyurea required to make the disease reach complete or partial clinical hematological reaction, ANC600000/µL 2 Use any dose of hydroxyurea, PLT > 400000/µLand WBC 400000/µLand Hb 400 × 109/LWBC>10x109/L) 3 After treatment, the palpated giant spleen failed to shrink by more than 50% or the clinical symptoms related to splenomegaly failed
Exclusion criteria
Exclusion criteria: 1) The toxicity reaction of previous anti-tumor treatment has not recovered to level I or below (except for the toxicity that the researcher judged to have no safety risk, such as unsolvable stable chronic toxicity, peripheral neurotoxicity, etc.); 2) Patients who have undergone splenectomy in the past or who have received splenic radiotherapy within 3 months before screening; 3) Screening patients who have undergone surgery or have not recovered from surgery within the first 4 weeks; 4) Patients with other malignant tumors within 5 years, except those with cured melanoma, skin cancer and carcinoma in situ; 5) Those with factors that may affect the absorption of oral drugs (such as inability to swallow, postoperative gastrointestinal resection, chronic diarrhea and intestinal obstruction); 6) Patients suffering from serious mental illness or unable to stop using psychotropic and sedative drugs; 7) Active or uncontrolled serious infection; 8) Patients with congestive heart failure of grade III or above (NYHA grade), uncontrolled or unstable angina pectoris or myocardial infarction, arrhythmia (female QTc>470ms, male QTc>450ms), cerebrovascular accident or pulmonary embolism and other thrombotic diseases within 6 months before screening; 9) Hypertension that cannot be controlled after drug treatment (systolic blood pressure = 150 mmHg, diastolic blood pressure = 100 mmHg); 10) HBsAg positive and HBV-DNA detection = the upper limit of normal value; HCV antibody is positive; HIV antibody positive; 11) Patients with immunodeficiency (those with acquired or congenital immunodeficiency diseases or a history of organ transplantation); 12) Patients who have received other MPN treatment drugs within 2 weeks before the first administration, such as immunomodulatory therapy (such as interferon- a Prednisone or corticosteroids greater than 10 mg/day), radiotherapy and erythropoietin, androgen, thrombopoietin or granulocyte colony stimulating factor, or patients within the half-life of 6 drug elimination; 13) Known history of alcohol/drug abuse; 14) Have taken strong or moderate CYP3A inhibitors (such as ketoconazole, clarithromycin, itraconazole, nefazodone, thalithromycin, verapamil) or strong CYP3A4 inducers (such as rifampicin, carbamazepine, phenytoin sodium) within 1 week before the first administration; 15) Those who use grapefruit, carambola or their products and other special diets that may affect the absorption, distribution, metabolism and excretion of drugs within 48 hours before the first administration; 16) Suspected to be allergic to Lucotinib or similar drugs; 17) The blood pregnancy test of pregnant and lactating women or fertile women during screening period was positive; 18) Male subjects and female subjects of childbearing age who are unwilling to take effective contraceptive measures within 6 months from the signing of the informed consent form to the last administration; 19) Those who have participated or are participating in other clinical trials within one month; 20) The investigator judged that the patient needed one or more treatments that would interfere with the primary endpoint or other conditions that were not suitable for the clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose;safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic characteristics;availability; | — |
Countries
china
Contacts
Public ContactChunkang Chang
Shanghai Sixth People's Hospital
Outcome results
None listed