ACCL1931

Summary

This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. In adolescents and young adults, liver toxicity from asparaginase is common and often prevents the delivery of planned chemotherapy—which could potentially compromise outcomes. Some people may also be at a higher risk for developing liver damage due to fatty presence in the liver or demographics. Carnitine naturally occurs in the body and is necessary for metabolism and its deficiency or absence is associated with liver or other organ damage. Levocarnitine is a drug used to provide extra carnitine to potentially help prevent the liver from toxicity against asparaginase. 

Patients will be randomized to one of two arms:

• Arm 1: Levocarnitine is added to standard chemotherapy
• Arm 2: Standard chemotherapy

To be included in ACCL1931, participants must be / have 

• Greater than or equal to 15 years and less than 40 years old at time of diagnosis
• Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL)
• Conjugated bilirubin =< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (ALT) =< 225 U/L (=< 5x ULN) (within 7 days prior to enrollment)
• SGOT (AST) =< 250 U/L (=< 5x ULN) (within 7 days prior to enrollment)
• All patients and/or their parents or legal guardians must sign a written informed consent

To be included in ACCL1931, participants must not be / have

• 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.
• 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.

Keywords

Chemotherapy; Leukemia; Liver; Lymphoma