A Phase I Study of Duvelisib in Combination With Nivolumab for Patients With Richter's Syndrome and Transformed Follicular Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) of duvelisib
研究概览
简要总结
This phase I trial studies the side effects and best dose of duvelisib when given together with nivolumab in treating patients with Richter syndrome or transformed follicular lymphoma. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving duvelisib and nivolumab may work better in treating patients with Richter syndrome or transformed follicular lymphoma compared to giving duvelisib or nivolumab alone.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of duvelisib in combination with nivolumab for patients with Richter?s syndrome or transformed follicular lymphoma.
SECONDARY OBJECTIVES:
I. To assess preliminary efficacy of duvelisib in combination with nivolumab in Richter?s syndrome and transformed follicular lymphoma (overall response rate, progression free survival, overall survival).
II. To determine the toxicity profile of duvelisib in combination with nivolumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CLL or small lymphocytic lymphoma (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria AND biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), clinically consistent with Richter?s syndrome (RS) OR histologically diagnosed relapsed or refractory DLBCL including transformed follicular lymphoma (tFL) ineligible for or refractory to platinum containing salvage therapy for the dose escalation portion of the study. For the dose expansion phase only patients with CLL with transformation to DLBCL or tFL will be eligible
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) >= 500/uL
- •Platelet count >= 30,000/uL (unless due to bone marrow involvement)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 ULN
- •Total bilirubin =< 1.5 ULN (unless due to liver involvement, hemolysis, or Gilbert?s disease)
- •Creatinine clearance >= 40 mL/min (Cockcroft-Gault estimated)
- •Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug
- •Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
- •Patients must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
排除标准
- •Documented infection with human immunodeficiency virus (HIV) or chronic, active hepatitis B or C infection
- •Any chemotherapy or monoclonal antibodies within 14 days or kinase inhibitors (except BTKi) within 5 half-lives before cycle 1, day 1 (C1D1). BTK inhibitors may be continued until 2 days prior to C1D
- •Steroids are allowed for palliation of symptoms due to lymphoma
- •Toxicity from previous therapy which has not resolved to grade 1 (or patient?s previous baseline)
- •Other active malignancies except those treated with curative intent with no active disease at the time of study entry or those felt to be at low risk of progression or recurrence over the next 2 years (such as low risk prostate cancer on active surveillance)
- •New York Heart Association (NYHA) class III/IV heart disease or other significant medical condition or organ system dysfunction which could compromise the subject?s safety or put the study outcomes at undue risk
- •Uncontrolled systemic infection
- •Unable to swallow capsules or significant malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at the time of screening
- •Patients who are pregnant or breastfeeding
- •Patients with known central nervous system (CNS) involvement by CLL or lymphoma
- •Patients who have underwent autologous or allogeneic stem cell transplant =< 4 weeks prior to C1D1 or have active graft-versus-host disease are excluded
研究组 & 干预措施
Treatment (duvelisib, nivolumab)
Patients receive duvelisib PO BID on days 1-28 and nivolumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Duvelisib (Drug)
Treatment (duvelisib, nivolumab)
Patients receive duvelisib PO BID on days 1-28 and nivolumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Maximum-tolerated dose (MTD) of duvelisib
时间窗: Up to 28 days
The MTD is defined as the highest dose level where at most one patient out of six experiences dose-limiting toxicities.
次要结局
- Overall response rate(Up to 3 years)
- Overall survival (OS)(From cycle 1, day 1 to date of progression or death, assessed up to 3 years)
- Progression-free survival (PFS)(From cycle 1, day 1 to date of progression or death, assessed up to 3 years)
研究者
David Bond, MD
Principal Investigator
Ohio State University Comprehensive Cancer Center