A Three-Arm Study of ME-401 Monotherapy in Subjects With Relapsed/Refractory CLL, SLL, or FL, of ME-401 in Combination With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination With Zanubrutinib in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 97
- 试验地点
- 18
- 主要终点
- Minimum Biologically Effective Dose (mBED) of ME-401 alone
研究概览
简要总结
A Three-Arm Study of ME-401 in Subjects with Relapsed/Refractory CLL/SLL or FL, of ME-401 in Combination with Rituximab in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination with Zanubrutinib in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL
详细描述
This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME-401 alone, ME-401 plus rituximab, or ME-401 plus zanubrutinib based on disease type and availability of an open enrollment slot.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- •Known histological transformation from CLL to an aggressive lymphoma
- •Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
- •Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody
- •Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody
- •Ongoing drug-induced pneumonitis
- •History of clinically significant cardiovascular abnormalities
- •History of severe bleeding disorders (ME-401 plus zanubrutinib arm only)
- •Known central nervous system (CNS) hemorrhage or stroke within 6 months prior to start of study drugs (ME-401 plus zanubrutinib arm only)
研究组 & 干预措施
ME-401 Alone
This arm is an open-label, dose escalation study to determine the safety, efficacy and pharmacokinetics of ME-401 along with the mBED, MTD, and DLTs. There are 4 planned cohorts which may enroll up to 61 subjects.
干预措施: ME-401 (Drug)
ME-401 in Combination with Rituximab
The second arm is an open label study to evaluate the safety, efficacy, and pharmacokinetics of ME-401 in combination with rituximab in subjects with various B-cell malignancies. There are two planned cohorts which may enroll up to 30 subjects.
干预措施: ME-401 (Drug)
ME-401 in Combination with Rituximab
The second arm is an open label study to evaluate the safety, efficacy, and pharmacokinetics of ME-401 in combination with rituximab in subjects with various B-cell malignancies. There are two planned cohorts which may enroll up to 30 subjects.
干预措施: Rituximab (Drug)
ME-401 in Combination with Zanubrutinib
The third arm is an open label study evaluating the safety, efficacy, MTD, DLT and pharmacokinetics of ME-401 in combination with zanubrutinib in subjects with various B-cell malignancies. This arm will include 2 stages: a safety evaluation stage (cohort of 6-12 subjects) and a disease-specific expansion cohort stage (up to 74 subjects).
干预措施: ME-401 (Drug)
ME-401 in Combination with Zanubrutinib
The third arm is an open label study evaluating the safety, efficacy, MTD, DLT and pharmacokinetics of ME-401 in combination with zanubrutinib in subjects with various B-cell malignancies. This arm will include 2 stages: a safety evaluation stage (cohort of 6-12 subjects) and a disease-specific expansion cohort stage (up to 74 subjects).
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Minimum Biologically Effective Dose (mBED) of ME-401 alone
时间窗: 1 year
The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.
Maximally Tolerated Dose (MTD) of ME-401 alone
时间窗: 1 year
The MTD will be determined as the maximum dose that is safe. DLT rate closest to .25 and not to exceed 2 DLTs in 6 subjects
Determine the MTD of ME-401 plus zanubrutinib
时间窗: 1 year
The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.
Determine the DLTs of ME-401 plus zanubrutinib
时间窗: within the first 56 days
DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 plus zanubrutinib
Evaluate the safety and tolerability of ME-401 plus zanubrutinib
时间窗: 1 year
Safety and tolerability will be measured by the number of treatment related AEs
Dose Limiting Toxicities (DLTs) of ME-401 alone
时间窗: within the first 56 days
DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 administration, is considered clinically significant by the P.I. and occurs in the presence of supportive care
Evaluate the safety and tolerability of ME-401 plus rituximab
时间窗: 1 year
Safety and tolerability will be measured by the number of treatment related AEs
次要结局
- Evaluate the PK (Cmax) of ME-401 alone(2 years)
- Efficacy of ME-401 with rituximab(2 years)
- Evaluate the PK (AUC) of ME-401 with rituximab(2 years)
- Evaluate the PK (Cmax) of ME-401 with rituximab(2 years)
- Efficacy of ME-401 with zanubrutinib(2 years)
- Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib(2 years)
- Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib(2 years)
- Safety profile of ME-401 alone(1 year)
- Efficacy of ME-401 alone as assessed by (OR)(2 years)
- Evaluate the (AUC) PK of ME-401 alone(2 years)