A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A (Apilimod Dimesylate Capsules) Administered Orally in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 10
- 主要终点
- Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
研究概览
简要总结
This is a Phase 1 dose-exploration study of LAM-002A administered by mouth in patients with relapsed or refractory B-cell NHL. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),and preliminary anti-tumor activity will be evaluated.
详细描述
LAM-002A is supplied as 25-mg or 50-mg capsules and will be administered two times daily or three times daily by mouth in repeated 28-day cycles. Patients will be advised to take the doses at the same time each day.
A 3 + 3 design will be utilized to define a maximum tolerated dose (MTD). The MTD is defined as the highest dose at which no more than 1 of 6 patients (i.e., < 33%) experiences a dose-limiting toxicity (DLT) in the dose cohort.
Once the dose and schedule are established, additional patients will be treated to better characterize the safety, tolerability,PK, PD, and anti-tumor activity of LAM-002A when administered alone or in combination with rituximab or atezolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Able to understand and comply with the protocol requirements and has signed the informed consent document.
- •Confirmed diagnosis of B-cell Non-Hodgkin's lymphoma limited to follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary mediastinal B-cell lymphoma (PMBL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has progressed and for which standard curative measures do not exist or are no longer effective. Prior therapy must have included a rituximab-based regimen.
- •Patients with DLBCL: Cancer progression after transplant, or be unwilling, unable or not an appropriate candidate for an autologous stem cell or bone marrow transplant
- •Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of 1 or more lesions that measure at least 2.0 cm in the longest dimension (as assessed radiographically)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
- •Adequate organ and marrow function.
- •Able to swallow oral capsules without difficulty.
- •Acceptable birth control.
- •Women of childbearing potential : negative pregnancy test
- •Adequate archival or fresh tumor tissue (from biopsy, bone marrow, or peripheral blood) for analysis of potential predictive biomarkers.
排除标准
- •Patients with central nervous system (CNS) lymphoma are not eligible for the trial unless the disease had been treated and the subject remains without symptoms with no active CNS lymphoma.
- •Not recovered from toxicity due to all prior therapies.
- •Other uncontrolled significant illness.
- •History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of LAM-002A
- •Major surgery within 28 days prior to first dose of study drug.
- •Past history of tuberculosis (TB) or active infection with TB, human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
- •Lactation or breast feeding.
- •Unable or unwilling to abide by the study protocol or cooperate fully with the Investigator or designee.
- •This is a shortened list and additional criteria may apply.
研究组 & 干预措施
Continuous monotherapy
All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
干预措施: LAM-002A (Drug)
Intermittent monotherapy
All patients will receive LAM-002A at escalating dose levels two times daily by mouth for 3 days on therapy followed by 4 days off therapy every week until cancer progression or intolerability.
干预措施: LAM-002A (Drug)
LAM-002A + rituximab
All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and rituximab 375 mg/m2 by vein every week for 4 weeks and then every 8 weeks for 4 times (total of 8 infusions)
干预措施: Rituximab (Drug)
LAM-002A + atezolizumab
All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and atezolizumab 1200 mg by vein every 3 weeks until cancer progression or intolerability
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
时间窗: 28 days
MTD was determined by testing increasing doses up to 125 mg twice a day or 75 mg three times a day orally on dose escalation cohorts with 3 to 6 participants each. In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using a standard definition of MTD (ie, the highest starting dose associated with DLT in \<33% of subjects during the first cycle of therapy) when administered continuously (daily administration) and then when administered intermittently (repeated courses of 3 days on and 4 days off).
次要结局
- Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A(8 days)
- Peak Plasma Concentration (Cmax) of LAM-002A(8 days)
- Objective Response Rate(1 cycle (28 days) up to a maximum of 24 cycles)