safety, tolerability and pk of btk inhibitor dtrmwxhs-12 in patients with b-cell lymphomas

Conditions: Chronic Lymphocytic Leukemia; B-cell Lymphomas

Summary: the primary objective is to evaluate the safety and tolerability of multiple dose oral administration of dtrmwxhs-12 capsule in patients with b-cell lymphoma. the secondary objective is to evaluate the pharmacokinetics of multiple dose oral administration of dtrmwxhs-12 capsule in patients with b-cell lymphoma.


Eligibility criteria:
inclusion criteria: * age≥18 years, gender is not limited. patients are voluntary to sign the informed consent form. * b-cell lymphoma based on who classified definition: including chronic lymphocytic leukemia (cll)/ small lymphocytic lymphoma (sll); chronic lymphocytic leukemia with 17p-; mantle cell lymphoma (mcl); waldenstrom's macroglobulinemia(wm); diffuse large b-cell lymphoma (dlbl or dlbcl) etc. * measurable lesion: non-hodgkin 's lymphoma requires at least a two-dimensional lesion diameter ≥ 2 cm, chronic lymphocytic leukemia ≥ 5000 leukemia cells / mm3, waldenstrom's macroglobulinemia igm ≥ 1000 mg / dl, bone marrow lymph plasma -like cells infiltration, histopathologically diagnosed as diffuse large b- cell lymphoma. * investigator judges that the treatment is needed. * patients, who at least failed in lymphoma treatment once and without standard therapeutic options, can't satisfy the requirement or decline treatment or failed in autologous stem cell transplantation for diffuse large b- cell lymphoma. * ecog (eastern cooperative oncology group) performance status 0 \~1 * life expectancy greater than 4 months * ability to swallow capsules * hematologic functions satisfy: neutrophils ≥1.5×109 / l ( according to the investigators' opinion , if they judge that the patients' neutrophil count lower than this threshold, which caused by chronic lymphocytic leukemia and bone marrow infiltration, those patients are eligible to be included. ), platelet(plt) ≥75×109/l, hb≥80g/l * renal functions satisfy: creatinine (cr) ≤ 1.5 times of upper limit of normal persons; creatinine clearance rate≥50ml/min (estimated by cockcroft-gault formula or detected by nuclear medicine scan or 24 hours urine method) * liver functions satisfy: ast and alt≤2.5 times of normal value, bilirubin ≤1.5 times of normal value * coagulation function: international normalized ratio (inr) and aptt ≤ 1.5 times of normal value; * throughout the course of the study and 90 days of treatment interruption, female of childbearing age and fertile males who must take one of the following effective contraception measures: abstinence, barrier-type dual contraceptive methods, iuds, administration of hormonal contraception drug. * male subjects are prohibited sperm donation from the start to the end of treatment within 90 days. exclusion criteria: * patients with brain metastasis * disease with changes of pathological tissue types (including large cell transformation) * patients who received allogeneic stem cell transplantation within 6 months, or with organized incompatibility reaction (gvhd), requires immunosuppressive therapy * patients who received steroid anti-tumor therapy within 7 days, or receive chemotherapy within 2 weeks, or receive monoclonal antibody therapy within 4 weeks, prior to first administration of dtrmwxhs-12 capsule. * patients received other btk inhibitor therapy * patients had early received chemotherapy but their toxicity has not been cleared (according to nci-ctcae 4.03, unrecovered toxicity grade ≤1) * patients who received chinese herbal anti-tumor therapy within 1 week before the start of study * patient with a history of other malignant within 2 years before enrollment, except (1) adequately treated in situ cervical cancer;(2) local basal cell carcinoma or squamous cell carcinoma (3) local malignant tumor which has been completely treated (by surgery or other means) * patients with uncontrolled systemic infection requiring intravenous anti-infection treatment * patients received major surgery in the past 4 weeks * patients with hiv infection, hbs-ag positive * according to new york heart association (nyha) classification, patients with cardiovascular disease of grade ≥3 * patients with history of myocardial infarction, acute coronary syndrome (unstable angina), receiving coronary angioplasty and stent implantation within 6 months of study entry * patients applied something which may cause qt prolongation or accompany by torsades healer within 7 days prior to enrollment. * prolonged qtc interval (defined as a qtc\> 450 ms) or other significant ecg abnormalities, including second degree atrioventricular block type ⅱ, third degree atrioventricular block, or bradycardia (heart rate less than 50 beats / min),ecg qtc\> 450 milliseconds, the ecg may be submitted to expert for centralized evaluation * subjects, the investigators think whose existing renal disease, neurological / psychiatric disorders, liver or endocrine disorders could affect their participating in the experiment * subjects with poor compliance * subjects are using cyp3a inhibitors (or inducer)