A Study of GNC-035 in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies

Inclusion Criteria

• •1. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form;
• •2. No gender limit;
• •3. Age: ≥18 years old (≤75 years old for climbing);
• •4. expected survival time ≥3 months;
• •5. Patients with hematological malignancies such as relapsed/refractory chronic lymphocytic leukemia confirmed by histology or cytology;
• •6. For relapsed or refractory chronic lymphocytic leukemia (CLL/SLL), specifically:
• •Patients who have relapsed after at least one line of standard therapy or have no response to or intolerance to standard regimens; Patients with relapsed or refractory chronic lymphocytic leukemia who were not or were ineligible for/intolerant of other therapies according to investigator assessment.
• •Relapsed and refractory were defined as follows:
• •Relapse was defined as disease progression after a response to adequate treatment, including at least one regimen containing a BTK inhibitor.
• •Refractory was defined as refractory to BTK inhibitor, failure to achieve remission after adequate treatment with BTK inhibitor-containing regimens (combination therapy or monotherapy), or disease progression during treatment or within 6 months after completion of adequate treatment.
• •7. For other patients with relapsed refractory non-Hodgkin lymphoma. These include:
• •Patients who experience failure of at least two lines of therapy; Relapsed or refractory patients who are not or are ineligible for/intolerant of other therapies as judged by the investigator.
• •Relapsed and refractory were defined as follows:
• •Relapse was defined as disease progression after a response to adequate treatment, including at least one anti-CD20 monoclonal antibody.
• •Refractory was defined as refractory to anti-CD20 monoclonal antibody, failure to achieve remission after adequate treatment with anti-CD20 monoclonal antibody (combination therapy or monotherapy), or disease progression during treatment or 6 months after completion of adequate treatment.
• •Among them, "adequate treatment with anti-CD20 monoclonal antibody" refers to the completion of full cycle of anti-CD20 monoclonal antibody combined with chemotherapy according to pathological type and disease stage, or anti-CD20 monoclonal antibody monotherapy at a dose of 375 mg/m2 once a week for at least 4 injections. Progression during treatment required the completion of at least one cycle of anti-CD20 monoclonal antibody combined with chemotherapy or monotherapy if progression occurred during induction therapy. At least one dose was completed if progression occurred during maintenance therapy. "Response" included complete and partial responses.
• •8. CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; Or the long diameter of any lymph node lesion ≥1.5cm; Patients with non-Hodgkin's lymphoma had measurable disease at screening (nodal disease ≥1.5cm in the greatest dimension or extranodal disease \> 1.0cm in the greatest dimension).
• •9. ECOG ≤2;
• •10. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0 (except alopecia);
• •11. Organ function within 7 days before the first dose:
• •Bone marrow function (for patients with non-Hodgkin lymphoma only) : without blood transfusion, G-CSF (for 2 weeks), and medication correction within 7 days prior to screening; Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L if the subject has bone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L if the subject has bone marrow infiltration); Platelet count ≥75×109/L; Liver function: total bilirubin, ≤1.5 ULN (Gilbert's syndrome, ≤3 ULN), and aminotransferase (AST/ALT), ≤2.5 ULN (for those with liver tumor invasive changes, ≤5.0 ULN) without correction with hepatoprotective medication within 7 days before screening examination; Renal function: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥60 mL/ minute (based on center calculation criteria) Coagulation: activated partial thromboplastin time (APTT) ≤1.5×ULN Prothrombin time (PT) ≤1.5×ULN.
• •12. Female subjects of childbearing potential or male subjects with a fertile partner must use highly effective contraception from 7 days before the first dose until 12 weeks after the last dose. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose;
• •13. Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.