A Single-arm, Multi-center Phase II Trial of Bendamustine/Rituximab Induction Followed by Venetoclax and Rituximab Consolidation for the Frontline Treatment of Chronic Lymphocytic Leukemia (CLL)
概览
- 阶段
- 2 期
- 干预措施
- Bendamustine
- 疾病 / 适应症
- Chronic Lymphocytic Leukemia
- 发起方
- Nicole Lamanna
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) after the completion of all therapy
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 [del(17p)]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.
详细描述
This is a single arm multicenter phase II study using bendamustine-rituximab (BR) followed by venetoclax and rituximab for the upfront treatment of chronic lymphocytic leukemia (CLL). The activity, safety, and survival data have been presented previously for BR alone in patients with previously untreated disease and venetoclax alone in relapsed/refractory patients and those with high-risk disease. After pretreatment evaluation, patients will receive three cycles of BR followed by venetoclax via a five-week dose escalation to 400 mg daily. Once patients reach 400 mg of venetoclax daily, patients will receive six cycles (months) of rituximab as consolidation. Total time of venetoclax therapy will be 12 cycles and total time on therapy (BR plus venetoclax plus rituximab) will be 15 cycles. Responses and endpoints will be assessed after 3, 6, 9 (laboratory only), 12, 18, 24, 30, and 36 cycles. Minimal residual disease (MRD) testing will be done after 3, 6, 9, 12, 18, and 24 cycles via an 8-color flow cytometry panel. Bone marrow testing for MRD can be performed if the peripheral blood is MRD negative (or was MRD negative at the last test). Anti-infective prophylaxis against H. zoster and P. jiroveci will be mandated. Tumor lysis syndrome (TLS) prophylaxis with allopurinol and/or an alternative will be mandated.
研究者
Nicole Lamanna
Associate Clinical Professor of Medicine
Columbia University
入排标准
入选标准
- •Age ≥ 18 years of age.
- •Diagnosed with CLL
- •To be considered CLL, the subject must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells.
- •Histologic and immunophenotypic analysis should demonstrate small to moderate size lymphocytes with flow cytometry demonstrating a certain population of lymphocytes.
- •No prior therapy for their disease. Topical or inhaled corticosteroids are permitted for other medical conditions, ie asthma or dermatologic reasons.
- •Eastern Oncology Cooperative Group (ECOG) performance score of ≤
- •Subjects with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment on this protocol regardless of disease stage upon discussion with the principal investigator.
- •An absolute neutrophil count \> 1.0 109/L; hemoglobin \> 8 g/dL; or a platelet count \> 50 x 109/L (unless due to bone marrow failure).
- •Adequate hepatic function
- •activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5x the upper limit of reference ranges.
排除标准
- •Subjects who have been previously treated for CLL or small lymphocytic lymphoma (SLL), except with corticosteroids for symptom relief.
- •Treatment with any of the following within 7 days prior to the first dose of study drug:
- •Steroid therapy for anti-neoplastic intent
- •moderate or strong cytochrome P450 3A (CYP3A) inhibitors
- •moderate or strong CYP3A inducers
- •Subject has known allergy to both xanthine oxidase inhibitors and/or rasburicase.
- •Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.
- •Subject has evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- •Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- •Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
研究组 & 干预措施
BR followed by venetoclax and rituximab
Subjects will be on Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days, and Rituximab 375 mg/m2 on day 1 or days 1-2 for three cycles with each cycle being 28 days. Venetoclax will then be started in a step-wise fashion per the package insert.
干预措施: Bendamustine
BR followed by venetoclax and rituximab
Subjects will be on Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days, and Rituximab 375 mg/m2 on day 1 or days 1-2 for three cycles with each cycle being 28 days. Venetoclax will then be started in a step-wise fashion per the package insert.
干预措施: Venetoclax
BR followed by venetoclax and rituximab
Subjects will be on Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days, and Rituximab 375 mg/m2 on day 1 or days 1-2 for three cycles with each cycle being 28 days. Venetoclax will then be started in a step-wise fashion per the package insert.
干预措施: Rituximab
结局指标
主要结局
Overall response rate (ORR) after the completion of all therapy
时间窗: 15 months
Proportion of patients with reduction in tumor burden of a predefined amount