Clinical Study of Orelabrutinib Combined With BG Regimen First-line Treatment of CLL/SLL

Официальное название

Exploratory Clinical Study of Orelabrutinib in Combination With BG Regimen in Patients With Naive and Unfit CLL/SLL Without 17p- or TP53 Mutations

Обзор

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• The rate of CR and uMRD [Срок оценки: Approximately 2 years.]

Вторичные конечные точки (4)

• The rate of CR/CRu and uMRD [Срок оценки: Approximately 2 years.]
• The Rate of uMRD [Срок оценки: Approximately 2 years.]
• PFS（progression-free survival） [Срок оценки: Up to 8 years.]
• OS（overall survival） [Срок оценки: Up to 10 years.]

Критерии участия

Критерии включения

• 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:

• 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

• Biochemical examination should meet the following standards:

• TBIL<2.0× ULN, CLL/SLL liver involvement or confirmed Gilbert syndrome (normal direct bilirubin), total bilirubia ≤ 3 times ULN;
• ALT and AST <2.5×ULN (ALT and AST <5×ULN for CLL/SLL liver involvement);
• 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.

Критерии исключения

• 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:

• treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL disease;
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• The Central Hospital Of Wuan — Ухань
• Hunan Cancer Hospital — Чанша

Идентификаторы

NCT: NCT05918276 · NFEC-2023-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗