Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Primary Outcome #1
研究概览
简要总结
Acute lymphoblastic leukemia (ALL) is the most common cancer seen in pediatric oncology. The necessary chemotherapy for pediatric and adolescent and young adult (AYA) patients with ALL includes steroids, anthracyclines, asparaginase, and vincristine. One of the most hepatotoxic chemotherapy agents is asparaginase, with treatment-associated hepatotoxicity (TAH) observed in up to 60% of patients. The frequency of TAH is increased in overweight or obese patients of Latino heritage. Carnitine is a naturally-derived compound that is produced in the liver and kidneys; it is found in certain foods, such as meat, poultry, fish, and some dairy products. Endogenous carnitine transports long-chain fatty acids into the mitochondria, where they are oxidized to produce energy, and acts as scavengers of oxygen free radicals. Thus, carnitine can reduce oxidative stress and modulate inflammatory response. Levocarnitine is a supplement form of carnitine used typically in the care and management of patients with carnitine deficiency. Pediatric and AYAs with ALL will be given oral levocarnitine as a supplement during their initial phases of treatment, when the most hepatotoxic agents are administered, to determine if the incidence of liver toxicity can be reduced or eliminated.
详细描述
Primary Aims
- Prospectively evaluate whether the prophylactic use of levocarnitine during Induction and Consolidation (phases with asparaginase therapy) in ALL patients receiving treatment according to a Children's Oncology Group (COG) treatment protocol reduces hepatotoxicity.
- Demonstrate an association between ethnicity and liver function test abnormalities in children and AYAs with ALL. Specifically, that Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥ 3 elevated liver function tests is more prevalent in self-identified Latinos as compared to other ethnicities in a retrospective control group.
Secondary Aims
- Determine whether obesity or overweight status, as measured by body mass index, at diagnosis increases the risk of hepatic dysfunction.
- Quantify the disease response, based on the end of Induction minimal residual disease (MRD) in the bone marrow of patients receiving levocarnitine, compared to historical controls to determine that levocarnitine does not have a negative impact on MRD.
- Assess incidence of nonalcoholic fatty liver disease (NAFLD), via non-invasive ultrasound elastography, in pediatric and AYA patients newly diagnosed with ALL.
- Assess incidence of other known toxicities of asparaginase treatment, including hyper/hypoglycemia, hypertriglyceridemia, pancreatitis, and thrombosis that are CTCAE version 5.0 grade ≥ 3 with onset ≤ 30 days (or next dose if sooner) of asparaginase.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 5 to < 30 years
- •Newly diagnosed with ALL designated as NCI high-risk (HR) ALL
- •Treatment for ALL to be according to a Children's Oncology Group (COG) treatment protocol (on study or according to study)
- •Ability to take oral medications and willing to adhere to the levocarnitine regimen
排除标准
- •Known allergic reaction to levocarnitine or its components
- •Presence of severely compromised renal function or end-stage renal disease
- •Pregnancy or lactation
- •Warfarin therapy
- •History of seizures prior to ALL diagnosis
- •Known inborn error of metabolism
研究组 & 干预措施
Treatment Arm (single arm)
干预措施: Levocarnitine (Drug)
结局指标
主要结局
Primary Outcome #1
时间窗: 1.5 years
Calculate proportion of patients who experience hepatotoxicity, as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥ 3 elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total and direct bilirubin.
Primary Outcome #2
时间窗: 1.5 years
Calculate prevalence of hepatotoxicity in patients who self-identify as Latino or non-Latino, using laboratory assessments and self-reported measures of ethnicity and/or race.
次要结局
- Secondary Outcome #3(1.5 years)
- Secondary Outcome #1(1.5 years)
- Secondary Outcome #4(1.5 years)
- Secondary Outcome #2(1.5 years)