Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL)
Conditions
Interventions
Treatment group:HBW-3220capule
Control group:Bendamustine + rituximab/methylprednisolone sodium succinate + rituximab
Sponsors
Chinese Academy of Medical Sciences Hospital of Hematology
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >=18 years old. 2. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2. 3. Predicted survival of >=3 months, as judged by the investigator. 4. Patients with pathology-confirmed CLL/SLL were required to have both the presence of treatment indications (see Appendix II) and at least one measurable lesion, including peripheral B lymphocyte count >=5×10^9/L, radiologically confirmed lymphadenopathy (baseline LDi > 1.5cm), or hepatomegaly/splenomegaly directly due to CLL. 5. Treatment failure, relapse after remission, or intolerance after previous treatment with a covalent BTK inhibitor. 6. Hematologic status within 7 days before starting HBW-3220: (1) Absolute neutrophil count (ANC) >=0.75×10^9/L and no growth factors were required. Growth factors could be administered at any time before administration to reach the 0.75×10^9/L threshold if bone marrow involvement was present. (2) Platelet count >=50×10^9/L or >=30×10^9/L if bone marrow involvement occurs (platelet transfusion or growth factors not used within 7 days before administration); (3) hemoglobin >=80g/L, or >=60g/L if bone marrow involvement was present (blood transfusion or growth factors were allowed within 7 days before administration). 7. Coagulation function: activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) =40mL/min. 10. Any nonhematologic toxicity related to previous therapy should revert to grade 1 or normal (except alopecia according to NCI CTCAE version 5.0). 11. Voluntarily provide written informed consent and understand and agree to follow the trial regimen and visit plan.
Exclusion criteria
Exclusion criteria: 1) Prior treatment with any of the following: A. receipt of a nontargeted small-molecule chemotherapeutic agent, targeted therapy, antitumor immunotherapy, or investigational agent within 4 weeks or five half-lives, whichever was shorter, before the first study dose; b. Radiotherapy to bone marrow-containing regions of the pelvis, skull, sternum, or whole brain within 4 weeks before the first study dose; Other palliative local radiotherapy within 1 week; c. Use of Chinese medicine or Chinese patent medicine with anti-tumor effect within 1 week before the first study drug administration; d. receive steroid therapy within 2 weeks before the first study dose in excess of the following criteria: > 2.25 mg/ day or equivalent dexamethasone for nonneoplastic disease and > 5 mg/ day or equivalent dexamethasone for neoplastic disease; Topical, inhaled, or temporary use of glucocorticoids was allowed. e. An investigational drug with an unknown half-life was administered within 4 weeks before the first study dose. 2) received live vaccine within 4 weeks before the first study dose. 3) Planned concomitant use of other systemic antitumor therapies during the study. 4) patients required continuous use of anticoagulants such as warfarin or vitamin K antagonists within 4 weeks before or during the study, or had bleeding tendency or coagulopathy. 5) use of potent CYP3A4 inhibitors or inducers, or potent P-glycoprotein (P-gp) inhibitors within 7 days or 5 half life (the longer) prior to initiation of HBW-3220 treatment, including but not limited to: itraconazole, ketoconazole, clarithromycin, rifampicin, carbazepine, phenytoin, St. 6) major surgery (excluding vascular access placement, biopsy, or laser eye surgery) within 28 days before the first study dose. 7) allogeneic or autologous stem cell transplantation (SCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 6 months before starting HBW-3220 therapy. 8) have active, poorly controlled autoimmune cytopenias (e.g., idiopathic thrombocytopenic purpura [ITP]) requiring new treatment or a dose increase to maintain blood counts within 28 days before enrollment. 9) known or highly suspected Richter's transformation, prolymphocytic leukemia, or central nervous system involvement (including in patients with prior primary CNS lymphoma in complete remission). 10) clinically significant uncontrolled cardiovascular disease, defined as: a. unstable angina within 2 months before HBW-3220 initiation; b. myocardial infarction within 6 months before starting HBW-3220; c. Left ventricular ejection fraction (LVEF) 159mmHg or diastolic blood pressure > 99mmHg)." 11)QT intervals corrected according to Fridericia's formula (QTcF) were >=450 msec in men and =470 msec in women on at least two of three electrocardiograms (ECG) obtained during screening. QTcF was calculated using Fridericia's formula (QTcF) : QTcF=QT/ (RR^0.33). 12) a history of stroke or intracranial hemorrhage within 6 months before the first dose. 13) patients with malignant tumors other than CLL/SLL within 3 years before the first dose (except for local tumors that have been obviously cured or have not recurs in the past 3 years, such as basa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate,ORR;PK characteristics;Safety ;EORTC QLQ-C30 assessment; | — |
Countries
China
Contacts
Public ContactLugui Qiu; Keshu Zhou
Chinese Academy of Medical Sciences Hospital of Hematology
Outcome results
None listed