CLL-OBG: Clinical Study of Orelabrutinib Combined With BG Regimen First-line Treatment of CLL/SLL
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OBG
|
Drug: Orelabrutinib and BG
Drug: Orelabrutinib Orelabrutinib 200mg, po, qd，C2-C7. Twenty-eight days for a cycle.
Drug: BG Bendamustin 70mg/m2, IV, d2&d3 inC1, and then d1&d2 inC2-6.Twenty-eight days for a cycle.
Obintuzumab 100mg IV, d1, 900mg d2, 1000mg d8&d15 in C1, and then 1000mg/m2 IV, d1 in C2-6. Twenty-eight days for a cycle.
Other Names:
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Outcome Measures
Primary Outcome Measures
- The rate of CR and uMRD [Approximately 2 years.]
The proportion of patients with CR and undetectable peripheral blood/bone marrow minimal residual disease in the end of combination therapy. Patients with CRi are counted as CR.
Secondary Outcome Measures
- The rate of CR/CRu and uMRD [Approximately 2 years.]
The proportion of patients with CR/CRu and undetectable peripheral blood/bone marrow minimal residual disease in the end of combination therapy. Patients with CRi are counted as CR. CRu is defined as a large spleen size of 16cm or less, and the rest of the indicators meet CR/CRi standards.
- The Rate of uMRD [Approximately 2 years.]
According to the detection of Shihe Gene [igNGS kit], no residual leukemia cells were detected in a million peripheral blood or bone marrow cells.
- PFS（progression-free survival） [Up to 8 years.]
Progression-free survival (PFS) is defined as the time from the date of first administration to the date of first disease progression or death from any cause, whichever occurs first.
- OS（overall survival） [Up to 10 years.]
Overall survival (OS) refers to the time from receiving the first dose to death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
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65 years of age and older or between 18 and 65 years of age with severe illness (non-CLL/SLL associated CIRS ≥ 6);
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ECOG performance status (PS) level 0~2；
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Expected survival is not less than 12 weeks;
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Chronic lymphocytic leukemia/small lymphocytic lymphoma diagnosed by flow cytometry or histopathology according to IWCLL2008 criteria, and CD20 positive;
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Meet at least 1 indication for treatment according to IWCLL2008 criteria or Chinese CLL/SLL guidelines 2022
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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);
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Have not received systematic treatment for CLL/SLL in the past;
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The main organs are functioning normally, the following criteria are met:
- 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
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Biochemical examination should meet the following standards:
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TBIL<2.0× ULN, CLL/SLL liver involvement or confirmed Gilbert syndrome (normal direct bilirubin), total bilirubia ≤ 3 times ULN;
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ALT and AST <2.5×ULN (ALT and AST <5×ULN for CLL/SLL liver involvement);
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Endogenous creatinine clearance ≥ 30 ml/min (Cockcroft-Gault formula).
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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;
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Subjects voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with follow-up.
Exclusion Criteria:
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Patients with 17P- chromosome abnormalities or TP53 mutations;
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Current or previous biopsy pathology confirms conversion to Richter's syndrome;
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Have active and uncontrolled autoimmune cytopenias, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura;
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Patients with central nervous system invasion;
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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:
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treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL disease;
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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;
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Previous or concurrent uncured malignant tumors, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix and superficial bladder cancer;
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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%;
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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;
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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.;
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Known hereditary or acquired bleeding and thrombosis (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
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Have undergone major surgical procedures or developed severe traumatic injuries, fractures or ulcers within 4 weeks of enrollment;
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Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction;
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Active infection requiring antimicrobial therapy (such as antibacterial drugs and antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment and antifungal treatment);
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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);
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Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders;
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Have participated in clinical trials of other antitumor drugs within 4 weeks before enrollment;
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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;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Central Hospital Of Wuan | Wuhan | Hubei | China | |
| 2 | Hunan Cancer Hospital | Changsha | Hunan | China |
Sponsors and Collaborators
- Nanfang Hospital, Southern Medical University
Investigators
- Study Chair: Ru Feng, Master, Nanfang Hospital, Southern Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NFEC-2023-202