A Phase I Clinical Trial to Determine the Safety and Tolerability of UC-961 (Cirmtuzumab), an Anti-ROR1 Monoclonal Antibody, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Who Are Ineligible for Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab
研究概览
简要总结
The purpose of the study is to investigate the safety of the investigational agent, cirmtuzumab. Cirmtuzumab is a monoclonal antibody drug designed to attach to a protein, called ROR1, on the surface of chronic lymphocytic leukemia (CLL) cells to block cell growth and survival. ROR1 is rarely expressed on healthy cells so the idea is to preferentially get rid of the cancer cells. Although there is evidence in laboratory animals that cirmtuzumab can decrease the number of CLL cells, the investigators do not know if this will work in humans. This drug will be given to humans for the first time in this study. Therefore, the goal of this study is to see if cirmtuzumab is safe and tolerated in study participants.
详细描述
This is a first in human, open-label single institution, Phase I dose escalation study of in patients with relapsed or refractory CLL. Treatment cycle (14 days) will consist of cirmtuzumab administered intravenously on a bi-weekly (every two weeks) schedule for a total of 4 doses. Eight dose cohorts (of 3 to 6 patients in size) plus an expansion cohort of 6 patients are planned. In the first 4 dose cohorts, there is intra-patient dose escalation to monitor for acute toxicities, such as tumor lysis syndrome.
A cycle may be repeated every 14 days if the patient has at least stable disease by clinical examination (or interim response assessment) and has again met hematologic, renal, and hepatic laboratory parameters as defined in the eligibility section, and is without ongoing Grade 3 non-hematologic or Grade 4 hematologic toxicities attributable to cirmtuzumab. The total duration of study drug administration is 4 cycles. Each cycle consists of clinical and laboratory evaluation on Day 1 and safety assessments on Days 3 and 8.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（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
- 未提供
研究组 & 干预措施
Cirmtuzumab 0.015 - 0.03 mg/kg
Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg
Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 0.5 - 1.0 mg/kg
Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 2.0 - 4.0 mg/kg
Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 8 mg/kg
Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 16 mg/kg
Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion
干预措施: cirmtuzumab (Drug)
Cirmtuzumab 20 mg/kg
Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
干预措施: cirmtuzumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab
时间窗: 1 year
The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.
Rate of Dose Limiting Toxicities (DLTs)
时间窗: The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts
The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation): 1. Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction. 2. Grade 4 neutropenia lasting more than 5 days despite appropriate medical management. 3. Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion. 4. Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC). 5. Grade 4 anemia unexplained by underlying disease. 6. Any AE requiring a dose delay of greater than 14 days. 7. Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.
次要结局
- Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.(From the start of investigational treatment to completion of follow-up, an average of 33 weeks)
- Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria(From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days)
- Progression Free Survival as Determined by iwCLL Criteria(From start of treatment until objective tumor progression or death)
研究者
Thomas Kipps
Deputy Director of Research Operations, Moores Cancer Center
University of California, San Diego