An Open-label, Dose Escalation, Phase I Study of IMC-EB10 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Maximum Tolerate Dose (MTD) of IMC-EB10
研究概览
简要总结
The purpose of this study is to determine if IMC-EB10 is safe for participants with leukemia, and also to determine the best dose of IMC-EB10 to give to participants.
详细描述
The purpose of this study is to define the maximum tolerated dose (MTD) and the pharmacokinetic (PK) profile of the anti-FMS-like tyrosine kinase 3 (FLT3) monoclonal antibody IMC-EB10, administered weekly in participant with acute lymphoblastic leukemia (AML) who have failed to achieve complete remission to a standard induction regimen, relapsed after response to previous antileukemia therapy, or are not eligible for potentially curative or approved salvage options.
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
- •The participant has acute myeloid leukemia in the bone marrow or blood that has relapsed with or without a prior complete remission
- •The participant is not regarded to be a candidate for a potentially curative, higher priority treatment for acute myeloid leukemia
- •The participant has resolution of all clinically significant toxic effects of any prior antitumor therapy and any other study-specific clinical or laboratory parameter specified in the entry criteria
- •The participant has not had major surgery, an open biopsy, a significant injury, and/or prior antitumor therapy (except antileukemia therapy) within 21 days prior to the first infusion of IMC-EB10
- •The participant has an Eastern Cooperative Oncology Group (ECOG)performance status of 0, 1, or 2 at study entry.
- •The participant is age 18 years or older
- •The participant has a life expectancy of >3 months
- •The participant has adequate liver and kidney function, as defined in the entry criteria
- •The participant is using an effective contraception (per the institutional standard), if procreative potential exists
- •The participant is able to give written informed consent
- •The participant is willing and able to comply with study procedures, scheduled visits, and treatment plans
排除标准
- •The participant has had prior allogenic or autologous stem cell transplant within <3 months of the first infusion of IMC-EB10
- •The participant has had an organ transplant (nonhematologic) within 3 years of study entry
- •The participant has active central nervous system leukemia
- •The participant has extramedullary disease without peripheral/and or bone marrow involvement
- •The participant is disease-free from a previous or concurrent malignancy for a period ≤ 1 year. A participant who has basal cell carcinoma or carcinoma in situ of the cervix will not be excluded from the study
- •The participant is currently receiving antileukemia therapy. Concurrent treatment with hydroxyurea is permitted
- •The participant has uncontrolled intercurrent illness as specified in the study entry criteria
- •The participant is receiving chronic steroid or other immunosuppressive medications. Occasional use of steroid-containing medications for, for example (e.g.), asthma exacerbation or for skin lesions, is permitted
- •The participant is receiving full-dose heparin (including low molecular weight heparin) or warfarin. [The participant is permitted to use low-dose warfarin to maintain patency of preexisting, permanent, indwelling intravenous (I.V.) catheters.]
- •The participant is pregnant (confirmed by urine or serum pregnancy test) or breast feeding
- •The participant has received treatment with monoclonal antibodies within 6 weeks prior to first infusion of IMC-EB10
- •The participant has a history of clinically significant allergic reactions to monoclonal antibodies or other therapeutic proteins
结局指标
主要结局
Maximum Tolerate Dose (MTD) of IMC-EB10
时间窗: Cycle 1 (28-day cycle)
MTD is defined as the dose preceding the dose level at which 2 participants experienced a dose limiting toxicity (DLT) during Cycle 1. DLT is defined using National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v 3.0): (1) any Grade 3 or 4 toxicity that is clearly not attributable to leukemia \[for example (e.g.) a type of end-organ failure that is infrequently encountered in acute myeloid leukemia (AML)\] and is possibly, probably, or definitely attributable to IMC-EB10 in the judgment of the investigator; and (2) any Grade 3 or 4 toxicity that is clearly not attributable to a co-medication (e.g., prolonged neutropenia that is not attributable to hydroxyurea).
次要结局
- PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)](Cycle 1 Week 1: predose, immediately after infusion, and at 1.5, 2, 4, 8, 24, 96 and 168 h after infusion ends (28-day cycle))
- PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours(Cycle 1 Week 3: predose, immediately after infusion and at 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycle))
- Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10)(8 weeks and 30-day post-treatment follow-up)
- Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response(Week 4 and Week 8)
- Pharmacokinetic (PK): Maximum Concentration (Cmax)(Cycle 1 Week 1: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 96, and 168 h after infusion ends, and Cycle 1 Week 3: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycles))
- Number of Participants With Anti-IMC-EB10 Antibodies(Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles))
- Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR)(4 weeks)