PRIMARY OBJECTIVE:~I. To determine in a randomized manner whether the addition of levocarnitine prophylaxis to asparaginase-containing regimens will decrease the incidence of conjugated hyperbilirubinemia (> 3 mg/dL) during acute lymphoblastic leukemia (ALL) induction therapy for adolescents and young adults (adolescents and young adults [AYAs], age 15-39 years).~SECONDARY OBJECTIVES:~I. To examine the impact of levocarnitine prophylaxis on differences in the incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during ALL Induction.~II. To compare rates of minimal residual disease (MRD) positivity at end of Induction and describe MRD+ by end of consolidation (EOC) in those receiving ALL induction chemotherapy with and without levocarnitine.~EXPLORATORY OBJECTIVES:~I. To compare rates of toxicity and associated dose reductions for chemotherapy administered with and without concomitant levocarnitine supplementation.~II. To compare across study arms the peak levels during Induction of conjugated and total bilirubin, AST, ALT, and duration of conjugated hyperbilirubinemia from onset > 3 mg/dL to =< 3 mg/dL.~III. To describe the efficacy of levocarnitine prophylaxis to reduce the incidence and/or severity of early patient-reported chemotherapy-induced peripheral neuropathy.~IV. To describe the three-year event-free and overall survival (EFS/OS) in those treated with and without levocarnitine prophylaxis.~V. To examine the association of age with asparaginase activity and asparaginase-associated hepatotoxicity during induction.~VI. To examine the association of body-mass-index (BMI) percentile (or absolute BMI for young adults) with asparaginase activity and asparaginase-associated hepatotoxicity during induction.~VII. To describe adherence by self-report and pill-count to oral levocarnitine in patients randomized to the intervention arm.~VIII. To examine the association of plasma levels of carnitine and related markers with the efficacy of levocarnitine supplementation.~IX. To determine the impact of inherited genetic variation on hepatoxicity and levocarnitine efficacy.~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM A: Patients receive levocarnitine orally (PO) or intravenously (IV) prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.~ARM B: Patients receive standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.~ARM C (RESCUE): Patients in Arms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO or IV supplementation until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).
This phase III trial compares the effect of adding levocarnitine to chemotherapy versus chemotherapy alone in protecting the liver in patients with leukemia and lymphoma. Standard of care chemotherapy treatment for leukemia and lymphoma includes a type of chemotherapy named asparaginase, given either as the drug pegaspargase, or a similar drug, calaspargase pegol. This type of chemotherapy can cause severe liver damage. Levocarnitine is a drug used to provide extra carnitine, a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is important to keep the liver healthy and may be able to prevent damage to the liver from chemotherapy and other drugs. Taking levocarnitine may reduce the rate of severe liver damage caused by asparaginase chemotherapy in patients with leukemia and lymphoma.