Phase IV Observational Study of Orelabrutinib in the Treatment of Chronic Lymphocytic Leukemia/Small Cell Lymphoma

Recruiting

• Conditions: CLL/SLL

• Registration Number: NCT05920668
• Lead Sponsor: Wang Xin

Brief Summary

This was a multicenter observational study of Orelabrutinib in the treatment of CLL/SLL. Patients were treated with Orelabrutinib for 12 cycles. The primary end points were grade 3 hypertension and incidence of atrial fibrillation, and the secondary end points were improvement in abnormal markers, ORR,CR,PFS, and OS.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-06-05
• Study First Submitted QC: 2023-06-16
• Last Update Submitted: 2023-06-16
• Study First Posted: 2023-06-27
• Last Update Posted: 2023-06-27
• Study Start: 2023-07-01
• Primary Completion: 2024-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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:

  2. 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;

  3. 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:

  2. Treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL disease;

  3. 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:

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  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) &lt 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 &gt; 470ms, male &gt; 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 &gt; 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The incidence of Grade 3 hypertension and atrial fibrillation	at the end of 12 cycles of treatment（(each cycle is 28 days)	Number of patients with grade 3 or above hypertension during treatment/total number of patients enrolled; number of patients with atrial fibrillation during treatment/total number of patients enrolled.

Secondary Outcome Measures

Name	Time	Method
ORR	at the end of 12 cycles of treatment(each cycle is 28 days)	Objective Response Rate
CR	at the end of 12 cycles of treatment(each cycle is 28 days)	complete response
PFS	From the date of receipt of the first investigational medication to the date of first onset of disease progression or death from any cause, whichever comes first.up to 2 years	progression-free survival
Improvement rate of abnormal indicators	After 12 cycles of treatment(each cycle is 28 days)	Continuous improvement in hematology (hemoglobin level increased to greater than 110g /L or ≥20 g/L increase from baseline, or platelet count increased to ≥50% from baseline, without blood transfusion/growth factors)
OS	From the date of receipt of the first study medication to the date of death from any cause.up to 2 years	Overall Survival
QoL	at the end of 12 cycles of treatment(each cycle is 28 days)	Quality of Life score

Trial Locations

Locations (1)

Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University; 🇨🇳 Jinan, Shandong, China