Clinical trial NCT05918276: Clinical Study of Orelabrutinib Combined With BG Regimen First-line Treatment of CLL/SLL
Official title: Exploratory Clinical Study of Orelabrutinib in Combination With BG Regimen in Patients With Naive and Unfit CLL/SLL Without 17p- or TP53 Mutations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: CLL/SLL
Keywords: Orelabrutinib
bendamustine
obintuzumab
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2023-06-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the treatment of navie CLL/SLL with orelabrutinib, bendamustine and obinutuzumab . The primary endpoint is the rate of CR and uMRD, and the second endpoints are survival time (OS and PFS) and toxicities.


Eligibility criteria: Inclusion Criteria:

* 65 years of age and older or between 18 and 65 years of age with severe illness (non-CLL/SLL associated CIRS ≥ 6);
* ECOG performance status (PS) level 0\~2；
* Expected survival is not less than 12 weeks;
* Chronic lymphocytic leukemia/small lymphocytic lymphoma diagnosed by flow cytometry or histopathology according to IWCLL2008 criteria, and CD20 positive;
* Meet at least 1 indication for treatment according to IWCLL2008 criteria or Chinese CLL/SLL guidelines 2022
* Enhanced computed tomography/magnetic resonance imaging (CT/MRI) to detect measurable lesions: at least one lymph node with a maximum axis of more than 1.5 cm and one measurable vertical dimension; for patients with chronic lymphocytic leukemia, only peripheral circulating lymphocyte count must be \> 5000/μL (or 5×10\^9/L);
* Have not received systematic treatment for CLL/SLL in the past;
* The main organs are functioning normally, the following criteria are met:

  1. Routine blood test standards should meet:

     Absolute neutrophil (ANC) ≥1.0×109/L, platelet (PLT) ≥30×109/L; unless bone marrow and hematopoietic insufficiency is confirmed to be due to CLL/SLL
  2. Biochemical examination should meet the following standards:

     1. TBIL\<2.0× ULN, CLL/SLL liver involvement or confirmed Gilbert syndrome (normal direct bilirubin), total bilirubia ≤ 3 times ULN;
     2. ALT and AST \<2.5×ULN (ALT and AST \<5×ULN for CLL/SLL liver involvement);
     3. Endogenous creatinine clearance ≥ 30 ml/min (Cockcroft-Gault formula).
* Women of childbearing age must have taken reliable contraceptive measures or have taken a pregnancy test (serum or urine) within 7 days prior to enrollment, have a negative result, and be willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the test drug. For men, consent to appropriate methods of contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug must be agreed;
* Subjects voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

* Patients with 17P- chromosome abnormalities or TP53 mutations;
* Current or previous biopsy pathology confirms conversion to Richter's syndrome;
* Have active and uncontrolled autoimmune cytopenias, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura;
* Patients with central nervous system invasion;
* Glucocorticoid therapy (at a dose equal to or greater than 20 mg/day of prednisone or equivalent) within 14 days prior to the first dose, excluding inhalation, topical medication, intra-articular medication, and prophylaxis before or after iodine contrast use; After discussion with the team leader, higher doses, longer steroid therapy may be allowed in the following cases:

  1. treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL disease;
  2. Acute exacerbations due to short-term (within 14 days) use of inactive infections for diseases not associated with CLL/SLL (e.g., arthritis, asthma), including steroid dose adjustment required for adrenal insufficiency;
* Previous or concurrent uncured malignant tumors, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix and superficial bladder cancer;
* Suffering from the following cardiovascular diseases: grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval QTc \>480ms); According to NYHA standards, grade III.\~IV. cardiac insufficiency, or cardiac ultrasound showed left ventricular ejection fraction (LVEF) \< 50%;
* Coagulation dysfunction (INR\>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), bleeding tendency or receiving thrombolysis or anticoagulation therapy;
* Arteriovenous thrombotic events that occurred within 12 months before enrollment, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
* Known hereditary or acquired bleeding and thrombosis (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
* Have undergone major surgical procedures or developed severe traumatic injuries, fractures or ulcers within 4 weeks of enrollment;
* Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction;
* Active infection requiring antimicrobial therapy (such as antibacterial drugs and antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment and antifungal treatment);
* Active hepatitis B (HBV DNA≥2000 IU/mL or 10000 copy number/mL) or hepatitis C (positive for hepatitis C antibodies and HCV RNA above the lower limit of the assay);
* Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders;
* Have participated in clinical trials of other antitumor drugs within 4 weeks before enrollment;
* Those who have received strong CYP3A4 inhibitor therapy within 7 days before enrollment, or received strong CYP3A4 inducer therapy within 12 days before participating in the study;
* Pregnant or lactating women; Patients of childbearing potential who are unwilling or unable to use effective contraception; 19. Other circumstances that may affect the conduct of clinical research and the determination of research results as determined by the investigator.

Primary outcomes:
measure: The rate of CR and uMRD
timeFrame: Approximately 2 years.
Secondary outcomes:
measure: The rate of CR/CRu and uMRD
timeFrame: Approximately 2 years.
measure: The Rate of uMRD
timeFrame: Approximately 2 years.
measure: PFS（progression-free survival）
timeFrame: Up to 8 years.
measure: OS（overall survival）
timeFrame: Up to 10 years.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: The Central Hospital Of Wuan
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Ru Feng, Master
role: STUDY_CHAIR
References: