Phase Ib Clinical Study of Keynatinib

The purpose of this study is to evaluate the efficacy, safety, PK characteristics in subjects with relapsed/refractory B-cell lymphoma. Furthermore, the relationship between the exposure level of Keynatinib and its efficacy and safety, the penetration rate of keynatinib in the Blood-Brain Barrier (BBB) and its PK characteristics in cerebrospinal fluid in R/R-PCNSL patients, the relationship between the BTK receptor occupancy rate and the efficacy are also evaluated.

Inclusion Criteria: 1. Unlimited gender, age ≥ 18 years (including critical value)-Cohort 1/2/3; 2. Voluntarily participate in the study and sign the ICF, follow the trial treatment protocol and interview plan-Cohort 1/2/3; 3. The subject's disease diagnosis meets all of the following conditions: Cohort 1: 1. Primary central nervous system lymphoma (PCNSL) confirmed by pathology; 2. For relapsed or refractory PCNSL, at least first line treatment must be given to Central Nervous System (CNS) lesions; 3. Brain Magnatic resonance Imaging (MRI) or Computerized tomography (CT) shows solid lesions of PD; Cohort 2: 1. CLL/SLL diagnosed according to IWCLL 2008 standards; 2. Refractory or relapsed CLL/SLL that previously received at least first-line systemic treatment. First-line treatment is defined as at least 2 cycles of standard protocol or clinical trial research protocol completed based on current guidelines; 3. Accord with at least one indication of CLL / SLL that requiring treatment; 4. There is medical record confirming that it is invalid or Progression Disease occurs after response for the latest treatment; 5. CT /MRI shows measurable lesions, which is defined as at least one lymph node with a maximum axis of more than 1.5 cm and with 2 measurable vertical dimension; 6. It is allowed to include the patients with a stable condition involving the central nervous system; Cohort 3: 1. Mantle cell lymphoma diagnosed by histopathology: including that t (11; 14) (q13; q32) positive by cytogenetic test and / or cyclin D1 highly expressed by immunohistochemistry; 2. Who have been pretreated with \> 1 but failed in ≤ 3 different chemotherapies and / or targeted drugs treatment. 3. There is a medical record confirming that it is invalid or Progression Disease occurs after response for the latest treatment; 4. CT / MRI shows measurable lesions, which is defined as the longest diameter (of ≥1 lymph node) \> 1.5 cm, and 2 vertical diameters is clearly measurable; 5. It is allowed to include the patients with a stable condition involving the central nervous system; 4. When screening, the status score of Eastern Cooperative Oncology Group (ECOG) is 0 to 2 points-Cohort 1/2/3; 5. Estimated survival time ≥ 4 months-Cohort 1/2/3; 6. Subjects have appropriate organ functions, the main organ functions meet the following criteria: 1. Blood routine: Neutrophil absolute value ≥ 1.0(in cohort1, 0.75 in cohort 2/3)×109 /L, platelet ≥ 75(in cohort1, 50 in cohort 2/3, 30×109/L are acceptable if CLL patients have bone marrow involvement, transfusion-dependent thrombocytopenia is excluded )×109 /L, hemoglobin ≥ 80 g/L(in cohort1). \[No blood transfusion and hematopoietic stimulating factor are used within 21 days (7 days in cohort 2/3) before the first administration-Chort1\]; 2. Blood biochemistry: Total bilirubin (TBIL) ≤ 2 × ULN (unless diagnosed as Gilbert syndrome), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × ULN; serum creatinine ≤ 2 × ULN or creatinine clearance rate ≥ 50 ml / min (calculated according to Cockcroft Gault formula)-Cohort 1/2/3; 3. Coagulation function: International Standardized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN-Cohort 1/2/3; 7. Fertile female subjects must agree to use contraceptives with an annual failure rate of \< 1% or maintain abstinence (avoid heterosexual intercourse) during the study and at least 90 days after the last administration of the study drug. Contraceptive methods with an annual failure rate of \