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

Overview

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.

Key Inclusion Criteria

For a patient to be eligible for participation in this study, all of the following criteria must apply.

• >= 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) (within 7 days prior to enrollment), and

  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50 U/L regardless of baseline

• SGOT (AST) =< 250 U/L (=< 5x ULN) (within 7 days prior to enrollment)

  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline
• Berlin-Frankfurt-Munich (BFM), Children’s Oncology Group (COG), or C10403-based Induction regimen and must be inclusive of >= 1 dose of pegaspargase or calaspargase pegol, and
• First dose of asparaginase must be planned within the first week of induction therapy, and

• Dose of pegaspargase or calaspargase pegol must be >= 1,000 IU/ m^2 (dose-capping permitted per primary regimen)

  • Note: Co-enrollment on a therapeutic consortia trial is not required
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Key Exclusion Criteria

A patient will not be eligible for this trial if any of the following criteria apply.

• Down syndrome
• Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other)
• Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig >= stage 3)

• Patients who received chemotherapy or treatment for a prior malignancy are not eligible

  • The following are permitted: steroid prophase, hydroxyurea, or other cytoreduction prior to initiation of Induction chemotherapy (must be documented) and chemotherapy for current diagnosis (i.e. initiation of Induction therapy within enrollment window). Chemotherapy prior to enrollment for treatment of a non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also permitted and must be documented
• Female patients who are pregnant since fetal toxicities and teratogenic effects in humans are unknown for study drug. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Sponsor(s)

Children’s Oncology Group

Learn More

To learn more, visit ClinicalTrials.Gov