ACCL1931: Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy

Asparaginase is an essential component of Induction chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). A deep remission following the initial induction phase, as evidenced by undetectable leukemia minimal residual disease (MRD), is a critical predictor of relapse and survival. However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often precludes delivery of planned chemotherapy, thereby potentially compromising outcomes. Carnitine is a natural occurring substance in the body necessary for ordinary metabolism and whose deficiency or absence is associated with liver and other organ damage. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase, but this has not yet been studied in a clinical trial. This open-label, randomized, controlled, Phase 3 trial will examine whether the addition of levocarnitine to asparaginase-containing induction chemotherapy regimens will reduce the rate of severe liver toxicity. In addition, for those who develop severe liver toxicity during Induction, levocarnitine will be made available to begin (or continue) to evaluate whether it is helpful to limit the severity and/or duration of the liver damage. Information gained from this trial will also improve future recommendations for asparaginase treatment by providing a better understanding of who is at risk for liver toxicity as well as the impact of liver toxicity on the patient experience, leukemia treatment response, relapse, and survival.