2023-504653-12-00招募中2 期
A PROSPECTIVE, OPEN-LABEL, MULTICENTRE PHASE-II-TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF ZANUBRUTINIB (BGB-3111), A BTK INHIBI-TOR, PLUS TISLELIZUMAB (BGB-A317), A PD-1 INHIBITOR, WITH AND WITH-OUT SONROTOCLAX (BGB-11417), A BCL2 INHIBITOR, FOR TREATMENT OF PATIENTS WITH RICHTER TRANSFORMATION - CLL-RT1-Trial
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 85
- 试验地点
- 11
- 主要终点
- Overall response rate (ORR) after induction therapy (i.e. 6 cycles) according to the refined Lugano Classification (Cheson et al, 2016). - Complete response (CR) - Partial response (PR)
研究概览
简要总结
The primary objective of the study is to evaluate the efficacy of a combinational therapy with tislelizumab and zanubrutinib in CLL patients with Richter transformation to DLBCL (cohort 1).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018)
- •Life expectancy ≥ 3 months
- •Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
- •Confirmed histopathological diagnosis of RT (diffuse large B-cell lymphoma or Hodgkin's lymphoma [Hodgkin's lym-phoma only when not eligible for more intensive treatment])
- •Previously untreated RT or patients with objective response or non-tolerance to first-line RT treatment
- •Adequate bone marrow function as defined by: - Absolute neutrophil count (ANC) ≥ 1000/mm3, except for patients with bone marrow involvement in which ANC must be ≥ 500/mm3 - Platelet ≥ 75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be ≥ 30,000/mm3
- •Creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection or an equivalent method
- •Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institu-tional ULN value, unless directly attributable to the patient’s CLL/RT or to Gilbert’s Syndrome, in which case a max. total bilirubin ≤ 3 x and AST/ALT ≤ 5 x the institutional ULN value are required. (For patients who start study treatment with elevated liver enzymes due to CLL/RT or Gilbert’s syndrome, toxicity and AE reporting will follow CTCAE grading once these values further increase. E.g. if a patient starts with a bilirubin value of 2.0 mg/dl, which rises to 3.0 mg/dl after one cycle, this should be reported as grade 2 bilirubinemia (see CTCAE v5))
- •Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every two months until 2 months after last dose of zanubrutinib), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
- •Age at least 18 years
- •ECOG performance status 0-2, ECOG 3 is only permitted if related to CLL or RT (e.g. due to anaemia or severe constitutional symptoms)
排除标准
- •Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients) ( In cases with urgent need for treatment, a prephase treatment with steroids, vincristine (up to 2 mg IV) or cyclo-phosphamide (up to 200 mg2 daily for max 3 days) can be administered at the discretion of the treating physician prior to enrolment or start of study medication. )
- •Requirement of therapy with phenprocoumon or other vitamin K antagonists.
- •Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows: - Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to under-go monitoring every 4 weeks for HBV reactivation. - Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV anti-body are eligible if HCV RNA is undetectable
- •Major surgery within 4 weeks of the first dose of study drug.
- •Any uncontrolled or clinically significant cardiovascular disease including the following: - Myocardial infarction within 6 months before screening - Unstable angina within 3 months before screening - New York Heart Association class III or IV congestive heart failure - History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ven-tricular fibrillation, torsades de pointes)
- •History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- •History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
- •Severe or debilitating pulmonary disease
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric sur-gery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- •Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration
- •Known hypersensitivity to tislelizumab, zanubrutinib, sonrotoclax or any of the excipients
- •Patients with more than one prior line of RT therapy
- •Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment)
- •Fertile men or women of childbearing potential unless: - surgically sterile or ≥ 2 years after the onset of menopause, or - willing to use two methods of reliable contraception including one highly effective contra-ceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 12 months after the end of study treatment.
- •Vaccination with a live vaccine <28 days prior to randomization
- •Legal incapacity
- •Prisoners or subjects who are institutionalized by regulatory or court order
- •Persons who are in dependence to the sponsor or an investigator
- •Allogenic stem cell transplantation within the last 100 days or signs of active GVHD after prior allogeneic stem cell transplantation within any time
- •Patients with confirmed PML
- •Uncontrolled autoimmune condition
- •Malignancies other than CLL currently requiring systemic therapies (unless the malignant disease is in a stable remission at the discretion of the treating physician)
- •Uncontrolled infection currently requiring systemic treatment
- •Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4, excluding the eyes/ears/nose/throat/larynx organ system , or any other life-threatening illness, medical condition or organ system dysfunction that – in the inves-tigator´s opinion could comprise the patients safety or interfere with the absorption or me-tabolism of the study drugs
- •Requirement of therapy with strong CYP3A4 inhibitors/ inducers
结局指标
主要结局
Overall response rate (ORR) after induction therapy (i.e. 6 cycles) according to the refined Lugano Classification (Cheson et al, 2016). - Complete response (CR) - Partial response (PR)
Overall response rate (ORR) after induction therapy (i.e. 6 cycles) according to the refined Lugano Classification (Cheson et al, 2016). - Complete response (CR) - Partial response (PR)
次要结局
未报告次要终点
研究者
Barbara Eichhorst
Scientific
University Of Cologne
研究点 (11)
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