Recurrent/refractory b-lymphocytic malignancy
Conditions
Interventions
cohort 1:100mg,qd,po
cohort 2:200mg,qd,po
cohort 3:300mg,qd,po
cohort 4:400mg,qd,po
cohort 5:500mg,qd,po
cohort 6:600mg,qd,po
cohort 7:300mg,qd,po
cohort 8:150mg, BID, po
Sponsors
The First Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients who voluntarily sign the informed consent and indicate the date of signature; 2. Aged >= 18 years, gender unlimited; 3. ECoG physical condition must be 0-2 points (refer to Appendix I); 4. Expected survival time >= 12 weeks; 5. Dose increase and dose exploration: patients who have received more than one previous standard anti-tumor treatment; Dose extension: (1) Relapsed or refractory CLL / SLL: CLL / SLL is diagnosed, relapse refers to complete or partial remission (PR), disease progression (PD) after >= 6 months; refractory refers to treatment failure (without PR) or PD after the last chemotherapy = 5.0 x 10^9 / L; for WM, IgM > 2 x ULN); 10. Patients with CLL / SLL diagnosed by flow cytometry or histopathology according to IWCLL2008 standard; 11. Patients with basically normal bone marrow function (without blood transfusion, G-CSF or medication correction within 14 days before screening), including: (1) ANC >= 1.0x10^9/l (CLL / SLL, MCL, MZL, FL, dlbc subjects with bone marrow infiltration should be >= 0.5 x10^9 / L); (2) Platelet count >= 75x10^9 / L (CLL / SLL, MCL, MZL, FL, dlbc subjects with bone marrow infiltration should be >= 50 x 10^9 / L); (3) Hgb >= 8.0g/dl (WM subjects, CLL subjects with bone marrow infiltration should be >= 7.0g/dl); 12. Patients with basically normal renal function, including: Serum creatinine = 60ml / min (according to the calculation standard of field measurement center); 13. Patients with normal liver function: (1) Serum total bilirubin = 1.0g/l; APTT <= ULN + 10s; Pt <= ULN + 3S; 15. The female subjects who are likely to be pregnant must carry out the serum pregnancy test within 7 days before the first medication, and the result is negative, and they are willing to use the efficient method of contraception during the study period and within 90 days after the last administration of the study drug. For male subjects whose partners are likely to be pregnant women, they should be sterilized by operation or agree to use
Exclusion criteria
Exclusion criteria: 1. Patients who have received treatment with the same mechanism compound (Btk inhibitor); 2. Patients who have received organ transplantation or allogeneic hematopoietic stem cell transplantation before; 3. Patients with central nervous system infiltration of lymphoma; 4. Patients who had undergone major surgery or severe trauma within 4 weeks before the first dose of study drug; 5. Patients who have received anti-tumor treatment (including chemotherapy, radiotherapy, immunotherapy, targeted therapy, traditional Chinese medicine or other clinical research treatment) within 4 weeks before the first dose of study drug; patients who have received anti-tumor treatment with steroid hormone (dose equivalent to prednisone > 30mg / day) within 14 days before the first dose of study drug; 6. Patients who are using strong inhibitors or inducers of CYP3A4 and CYP2C19; 7. Patients who need anticoagulation therapy such as warfarin or vitamin K antagonists, or who have bleeding tendency or coagulation disorder within 4 weeks before the first study drug administration or during the study period; 8. Patients with previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc; 9. Virological examination: HBsAg positive and HBV-DNA detection >= detection upper limit; HCV antibody positive and HCV-RNA >= detection upper limit of normal value; HIV antibody positive; 10. Patients with active infection found within 2 weeks before the first dose of study drug; 11. Patients with uncontrollable or important cardiovascular diseases, including: (1) Congestive heart failure (NYHA III or IV grade heart failure), myocardial infarction, unstable angina, or arrhythmia requiring treatment during screening, with left ventricular ejection fraction (LVEF) less than 50%, occurred within 6 months before the first administration of the study drug; (2) Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and atypical cardiomyopathy); (3) The clinical significance of QTc interval prolongation history, or screening period QTc interval (three times mean value) > 470msec (female) or > 450msec (male), QTCF = QT / (RR ^ 0.33); (4) Uncontrollable hypertension (systolic blood pressure >= 160mmhg and / or diastolic blood pressure >= 100mmhg in resting position after taking medicine); 12. Patients who had cerebrovascular accident and transient ischemic attack within 6 months before entering the study; 13. Patients with other malignant tumor history at the time of entry into the study (except for cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, breast ductal carcinoma in situ after radical surgery, and melanoma with complete remission > 5 years); 14. Patients who are unable to swallow or have active gastrointestinal inflammation, chronic diarrhea, known diverticulosis, or who have undergone gastrectomy or gastric banding. However, it is allowed to treat gastroesophageal reflux disease with proton pump inhibitor; 15. Patients with previous chronic pancreatitis, other pancreatic diseases, or blood amylase higher than 3 times of the upper limit of normal value; 16. Pregnant and lactating women, patients with family planning at this stage; 17. Subjects with other serious / severe acute or
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| PK;PD;ORR;DOR;PFS; | — |
Primary
| Measure | Time frame |
|---|---|
| MTD;DLT; | — |
Countries
China
Contacts
Public ContactJie Jin /Lihua Wu
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed