A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy
Children's Oncology Group
Summary
This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. Asparaginase is part of the standard of care chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often prevents delivery of planned chemotherapy, thereby potentially compromising outcomes. Some groups of people may also be at higher risk for liver damage due to the presence of fat in the liver even before starting chemotherapy. Patients who are of Japanese descent, Native Hawaiian, Hispanic or Latinx may be at greater risk for liver damage from chemotherapy for this reason. Carnitine is a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is necessary for metabolism and its deficiency or absence is associated with liver and other organ damage. Levocarnitine is a drug used to provide extra carnitine. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase. The overall goal of this study is to determine whether adding levocarnitine to standard of care chemotherapy will reduce the chance of developing severe liver damage from asparaginase chemotherapy in ALL, LL and/or MPAL patients.
Description
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 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 res…
Eligibility
- Age range
- 15–40 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * \>= 15 and \< 40 years at time of diagnosis * Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL) * Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use of tyrosine kinase inhibitors \[TKI\] or CRLF2- targeted concomitant medication must be documented, if used) * Conjugated bilirubin =\< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment), and * Serum glutamate pyruvate transaminase (SGPT) (ALT) =\< 225 U/L (=\< 5x ULN) (wit…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- DrugCalaspargase Pegol
Given standard of care calaspargase pegol
- Dietary SupplementLevocarnitine
Given PO or IV
- DrugPegaspargase
Given standard of care pegaspargase
- OtherQuality-of-Life Assessment
Ancillary studies
Locations (228)
- Children's Hospital of AlabamaBirmingham, Alabama
- Providence Alaska Medical CenterAnchorage, Alaska
- Kingman Regional Medical CenterKingman, Arizona
- Phoenix Childrens HospitalPhoenix, Arizona
- Banner University Medical Center - TucsonTucson, Arizona
- Arkansas Children's HospitalLittle Rock, Arkansas