A Phase 1 Open-Label, Dose-Ranging Safety and Pharmacokinetics Study of Oral Cladribine in Patients With Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Safety and Adverse Events (AEs)
研究概览
简要总结
The goal of Part 1 of this clinical research study is to find the highest tolerable dose of cladribine that can be given in combination with low dose cytarabine (LDAC) and venetoclax to patients who have AML.
The goal of Part 2 of this clinical research study is to learn if the dose of cladribine found in Part 1, when combined with LDAC and venetoclax, can help to control the disease.
详细描述
Primary Objective:
The primary objective of Phase 1 is to determine safety and tolerability of oral cladribine in patients with AML and to identify a RP2D.
Secondary Objective:
The secondary objectives of Phase 1 are to provide a qualitative assessment of systemic exposure based on plasma cladribine concentrations after administration of oral cladribine to patients with AML and to explore the activity of cladribine/LDAC/venetoclax in patients with relapsed or refractory AML.
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
- •Provision of written informed consent prior to any study related procedures.
- •Disease characteristics, defined as:
- •Dose-escalation cohorts: Patients with relapsed and/or refractory AML.
- •Cohort A: Patients aged .18 years with newly diagnosed ts-AML, defined as patients with prior diagnosis of MDS, treated with hypomethylating agents who have then progressed to AML. Prior therapy with hydroxyurea, hematopoietic growth factors, HMA, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed.
- •Cohort B: Patients aged . 60 years with newly diagnosed AML with monocytic phenotype, defined as AML-M5 by FAB or flow cytometry, and/or patients . 60 years with newly diagnosed AML with RAS mutations. Patients aged < 60 years who are unsuitable for standard induction therapy may be eligible after discussion with primary investigator.
- •Adequate renal and hepatic organ function as indicated by the following laboratory values:
- •Serum creatinine . 2.0xupper limit of normal (ULN)
- •Serum total bilirubin .2xULN (with the exception of patients with known Gilbert's syndrome: serum total bilirubin must be <3xULN in these patients)
- •Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) .2.5xULN or .5xULN if due to leukemic involvement)
- •Adequate cardiac function with a left ventricular ejection fraction .50%
- •Female participants are eligible to enter and participate in the study if they are of nonchildbearing potential. Female participants of childbearing age must use at least 2 forms of effective birth control during the study treatment period and for at least 90 days after the last dose of investigational product.
- •Male participants are eligible to enter and participate in the study if they agree to use effective methods of contraception during the study treatment period and for at least 90 days after the last dose of investigational product.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the compounds in the study.
- •Legal incapacity or limited legal capacity.
- •Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation.
- •Patients unwilling to comply with protocol requirements related to the assigned part.
- •Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy agents, breastfeeding should also be avoided.
研究组 & 干预措施
Part 1/2 Treatment with Oral Cladribine in Patients with Acute Myeloid Leukemia
Participants may be in the hospital up to the first 5 days on study to all monitoring for tumor lysis syndrome (TLS) and toxicities.
干预措施: Oral Cladribine (Drug)
Part 1/2 Treatment with Oral Cladribine in Patients with Acute Myeloid Leukemia
Participants may be in the hospital up to the first 5 days on study to all monitoring for tumor lysis syndrome (TLS) and toxicities.
干预措施: Cytarabine (Drug)
结局指标
主要结局
Safety and Adverse Events (AEs)
时间窗: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
次要结局
未报告次要终点