| Eligibility |
Inclusion Criteria:
- 1. Age 18-80 years old, gender unlimited; 2. Chronic lymphocytic/small cell leukemia
was confirmed by histopathology based on iwCLL criteria; 3. According to the iwCLL
standard, the treatment can be certified 4. IPI = 2 5. ECOG score =2 points; 6.
Measurable lesions detected by enhanced computed tomography/magnetic resonance imaging
(CT/MRI) : at least one lymph node with a maximum axis of more than 1.5cm and a
measurable vertical dimension; For patients with chronic lymphocytic leukemia, only
peripheral circulating lymphocyte count must be required. 5000/µL (or 5×10^9/L); 7. If
the major organs are functioning normally, the following criteria are met:
1. The standard of blood routine examination shall meet:
Neutrophil absolute value (ANC) =1.0×109/L, platelet (PLT) =30×109/L; Unless it
is confirmed that the bone marrow and hematopoietic deficiency is caused by
CLL/SLL;
2. Biochemical examination shall meet the following standards:
TBIL < 2.0×ULN, CLL/SLL involved liver or diagnosed Gilbert syndrome (normal direct
bilirubin), total bile red = 3 ULN; ALT and AST < 2.5×ULN (for CLL/SLL involved liver, ALT
and AST < 5×ULN); Endogenous creatinine clearance =30ml/min (Cockcroft-Gault formula). 8.
Women of childbearing age must have been using reliable contraception or have had a
pregnancy test (serum or urine) with negative results within 7 days prior to inclusion and
be willing to use an appropriate method of contraception during the trial period and 8
weeks after the last test drug administration. For males, consent is required to use an
appropriate method of contraception or surgical sterilization during the trial period and 8
weeks after the last administration of the trial drug; 9. Expected survival > 6 months; 10.
Patients voluntarily participated in this study and signed written informed consent.
Exclusion Criteria:
- 1. Patients who have received other BTK inhibitors in the past and have progressed; 2.
Patients with grade 3 hypertension 3. Patients with atrial fibrillation 4. Richter's
syndrome is or has been confirmed by biopsy pathology; 5. Has active and uncontrolled
autoimmune hemocytopenia, including autoimmune hemolytic anemia and idiopathic
thrombocytopenic purpura; 6. Present or past malignancies other than cured basal cell
carcinoma of the skin, carcinoma in situ of the cervix and superficial bladder
carcinoma; 7. Received glucocorticoid therapy (at a dose of 20 mg/ day or higher than
prednisone or equivalent) within 14 days prior to initial administration, except for
inhalation, topical, intraarticular, and prophylactic use before or after use of
iodized contrast agent; After discussion with the group leader, higher doses and
longer steroid therapy may be permitted in the following situations:
1. Treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with
CLL/SLL disease;
2. Short-term (within 14 days) use to treat non-active infections in diseases not
associated with CLL/ SRL (e.g., arthritis, asthma) to acute exacerbations,
including dose adjustments of steroids required for adrenal insufficiency; 8.
Patients who have undergone major surgical operations (tests for diagnostic
purposes) or participated in clinical trials of drugs/devices within 4 weeks; 9.
Have uncontrolled or significant cardiovascular disease, including:
1. New York Heart Association (NYHA) Class II or higher congestive heart failure,
unstable angina, myocardial infarction, or arrhythmia requiring treatment at the
time of screening, left ventricular ejection fraction (LVEF) < in the six
months prior to the initial administration of the study drug; 50%;
2. Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic
cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted
cardiomyopathy, unestablished cardiomyopathy);
3. Clinically significant history of prolonged QTc interphase, or women with
interphase QTc in screening period > 470ms, male > 450ms;
4. Subjects with symptomatic or medicated coronary heart disease;
5. Patients with uncontrolled hypertension (on the basis of improving their life
style, their blood pressure is still not up to the standard after more than 1
month with the application of reasonably tolerable enough 2 or more
antihypertensive drugs (including diuretics), or their blood pressure can be
effectively controlled by taking 4 or more antihypertensive drugs); 10. Abnormal
coagulation (INR > 1.5 or prothrombin time (PT) > ULN+4 s or APTT > 1.5 ULN)
or had active bleeding within 2 months prior to screening, or was taking
anticoagulant drugs, or had what the investigator considered a definite tendency
to bleed; 11. Arteriovenous thrombosis events, such as cerebrovascular accidents
(including temporary ischemic attack, cerebral hemorrhage, cerebral infarction),
deep vein thrombosis and pulmonary embolism, etc. occurred within 12 months
before enrollment; 12. Clinically significant gastrointestinal abnormalities that
may affect drug intake, transport, or absorption (e.g. inability to swallow,
chronic diarrhea, intestinal obstruction, etc.); 13. Active or uncontrolled HBV
(HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive; 14.
Uncontrolled, active systemic fungal, bacterial, viral or other infection
(defined as showing persistent signs/symptoms associated with the infection
despite no improvement with appropriate antibiotics or other treatment); 15.
Allergic disposition or hypersensitivity to obutinib or any other component of
the applicable investigational drug; 16. Those who have received potent CYP3A4
inhibitor therapy within 7 days before enrollment, or potent CYP3A4 inducer
therapy within 12 days before enrollment, or must also take CYP3A severely
inhibiting or strongly inducible drugs; 17. Those who have a history of
psychotropic substance abuse and cannot abstain or have mental disorders; 18.
Participated in clinical trials of other antitumor drugs within 4 weeks before
enrollment; 19. Pregnant and lactating women and subjects of childbearing age who
do not want to take contraceptive measures; 20. Poor compliance or inability to
follow up regularly; 21. Patients with life-threatening conditions or severe
organ dysfunction are deemed unfit to participate in the study; 22. The
investigator determines other circumstances that may affect the conduct of
clinical studies and the determination of study results.
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