Chronic lymphocytic leukemia/small lymphocytic lymphoma
Conditions
Interventions
Sponsors
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Subjects who meet the following inclusion criteria can be enrolled: (1) Patients with CLL/SLL confirmed by flow cytometry or histopathology per iwCLL 2018 criteria who have received first-line or above therapies, including patients with RR CLL/SLL who are intolerant to BTKis. (2) Subjects treated with ibrutinib or zanubrutinib monotherapy or in combination with CD20 monoclonal antibody, chlorambucil, or bendamustine as the last line therapy. (3) Male or female patients = 18 years old. (4) Subjects previously treated with ibrutinib and/or zanubrutinib and experienced any of the following are determined by the investigator as intolerant to ibrutinib and/or zanubrutinib, that the treatment should be terminated as judged by the investigator despite best supportive care: a) Hematologic toxicity = Grade 2 persists for > 14 days or recurs at least twice (with dose modification or interruption, as well as best supportive care); b) Non-hematologic toxicity = Grade 3; c) Grade 3 neutropenia complicated by infection or fever; d) Grade 4 hematologic toxicity; that the toxicity instead of PD results in termination of ibrutinib or zanubrutinib treatment. (5) Subjects whose ibrutinib and/or zanubrutinib-related toxicity decreases to = Grade 1 or to baseline before ibrutinib and/or zanubrutinib treatment (excluding alopecia). (6) Patients whose major organ function meets the following criteria: a) Hematology results: absolute neutrophil count = 0.75 × 109/L and platelets = 50 × 109/L in the absence of growth factor support therapy or blood transfusion within the last 7 days; b) Blood biochemistry: total bilirubin = 2 times the upper limit of normal (ULN) unless Gilbert syndrome is diagnosed; serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 times the ULN; serum creatinine = 1.5 times the ULN. (7) Subjects with ECOG performance status score = 2. (8) Subjects judged by the investigator to have a life expectancy greater than 12 weeks from screening. (9) Subjects willing and able to participate in all required assessments and procedures in the study protocol, including smooth swallowing of capsules. (10) Subjects (or legally acceptable representative of subjects) who understand and voluntarily sign the informed consent.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded: (1) Subjects with PD in CLL/SLL during any BTKi treatment. (2) Subjects with central nervous system (CNS) involvement or a history of such disease. (3) Subjects with current or previous Richter’s transformation. (4) Subjects with past history of malignant tumors, except in the following cases: a) Malignant tumors treated for curative purposes, with no evidence of active disease for more than 3 years prior to screening, and with a low risk of recurrence as judged by the treating physician; b) Adequately treated non-melanoma skin cancer or lentigo maligna melanoma with no evidence of disease at present; c) Adequately treated carcinoma in situ of cervix uteri with no evidence of disease at present. (5) Subjects previously treated with BCL-2 inhibitors. (6) Subjects treated with chemotherapy, radiotherapy, monoclonal antibody therapy, or corticosteroids (at doses equivalent to prednisone > 20 mg/day) for CLL/SLL from the use of the last BTKi treatment to the entry into this trial (corticosteroids must be discontinued for =2 weeks for the entry into the trial if used at a corresponding dose during this period). (7) Subjects with a history of intracranial hemorrhage or ischemic stroke within 6 months prior to the first dose of orelabrutinib. (8) Subjects with uncontrolled or significant cardiovascular diseases, including but not limited to: a) Congestive cardiac failure, unstable angina, or infarct myocardial of New York Heart Association (NYHA) class II or above, or arrhythmia requiring treatment at screening, left ventricular ejection fraction (LVEF) 470 ms in women and > 480 ms in men during the screening period. d) Uncontrolled hypertension. (9) Subjects with active hepatitis B or C infection. The result of polymerase chain reaction (PCR) prior to enrollment must be negative for subjects who are hepatitis B core antibody positive and hepatitis B surface antigen (HBsAg) negative. Patients who are HBsAg positive or PCR positive are excluded. (10) Subjects with known history of human immunodeficiency virus (HIV) infection. (11) Subjects with active bleeding within 2 months before screening, or the presence of a clear bleeding tendency as judged by the investigator (e.g., varices esophageal with bleeding risk, local active ulcer lesions). Subjects requiring anticoagulant therapy with warfarin or an equivalent vitamin K antagonist. (12) Subjects with uncontrolled active fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms associated with the infection that do not improve despite appropriate antibiotic or other treatment). (13) Subjects with obvious gastrointestinal dysfunction that may affect the intake, transport or absorption of drugs (e.g., inability to swallow, chronic diarrhoea, intestinal obstruction), or total gastrectomy. (14) Subjects with drug or alcohol abuse. (15) Subjects undergoing major surgery within 4 weeks prior to the first dose of the investigational drug. (16) Subjects requiring treatment with strong CYP3A inhibitors or inducers. (17) Subjects with clinical signs of brain dysfunct
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse events (AEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate(ORR);duration of response (DOR);progression-free survival (PFS);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactJianqing Mi
Department of Hematology, Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University
Outcome results
None listed