Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia

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:

The proposal is a non-randomized case-control pilot study that will use retrospective case-control data as comparison (i.e., control group).

Participants:

A sample of 20 pediatric and AYA patients, ages 5 to < 30 years, newly diagnosed with ALL will be enrolled to study. Participants who withdraw or who are withdrawn from study, who have taken less than 50% of planned levocarnitine supplementation, and who did not have a post-levocarnitine supplementation laboratory testing will be replaced. An additional 20 retrospective cases -- matched by age at diagnosis, biological sex, and risk classification at initial diagnosis -- will be included to provide control data.

Study Intervention:

Levocarnitine will be administered by mouth twice daily during Induction and Consolidation phases of treatment for patients with ALL who are treated as per a COG treatment plan (either on study or treated according to the protocol). The duration of intervention is expected to be approximately three months.

Inclusion criteria

• 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

Exclusion criteria

• 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