Health TrialsbyHealthPanel

Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia

ConditionsAcute Lymphoblastic LeukemiaHepatotoxicity
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age5-29
SponsorChildren's Hospital of Orange County

About this trial

Acute lymphoblastic leukemia (ALL) is the most common cancer seen in pediatric oncology. The necessary chemotherapy for pediatric and adolescent and young adult (AYA) patients with ALL includes steroids, anthracyclines, asparaginase, and vincristine. One of the most hepatotoxic chemotherapy agents is asparaginase, with treatment-associated hepatotoxicity (TAH) observed in up to 60% of patients. The frequency of TAH is increased in overweight or obese patients of Latino heritage. Carnitine is a naturally-derived compound that is produced in the liver and kidneys; it is found in certain foods, such as meat, poultry, fish, and some dairy products. Endogenous carnitine transports long-chain fatty acids into the mitochondria, where they are oxidized to produce energy, and acts as scavengers of oxygen free radicals. Thus, carnitine can reduce oxidative stress and modulate inflammatory response. Levocarnitine is a supplement form of carnitine used typically in the care and management of patients with carnitine deficiency. Pediatric and AYAs with ALL will be given oral levocarnitine as a supplement during their initial phases of treatment, when the most hepatotoxic agents are administered, to determine if the incidence of liver toxicity can be reduced or eliminated.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients aged 5 to < 30 years

Newly diagnosed with ALL designated as NCI high-risk (HR) ALL

Treatment for ALL to be according to a Children's Oncology Group (COG) treatment protocol (on study or according to study)

Ability to take oral medications and willing to adhere to the levocarnitine regimen

Disqualifiers

Known allergic reaction to levocarnitine or its components

Presence of severely compromised renal function or end-stage renal disease

Pregnancy or lactation

Warfarin therapy

Trial design

Design model

Single group

Treatments tested in this trial

  • Levocarnitine

    Drug

    Adults, or patients ≥ 50 kg: 990 mg PO (by mouth) bis in die (BID, twice a day) Children, or patients \< 50 kg: 50 mg/kg/day PO divided BID (maximum daily dose of 2,000 mg)

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: Treatment Arm (single arm)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Primary Outcome #1

Calculate proportion of patients who experience hepatotoxicity, as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥ 3 elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total and direct bilirubin.

Time frame
1.5 years
2

Primary Outcome #2

Calculate prevalence of hepatotoxicity in patients who self-identify as Latino or non-Latino, using laboratory assessments and self-reported measures of ethnicity and/or race.

Time frame
1.5 years

Secondary outcomes

1

Secondary Outcome #1

Calculate body mass index (BMI), from recorded height and weight obtained at time of initial diagnosis and determine if there is increased risk of hepatotoxicity in patients who are overweight or obese at diagnosis as determined by Centers for Disease Control and Prevention (CDC) clinical growth charts for study participants 5 to \< 20 years of age and by a BMI of ≥ 25.0 for study participants 20 to \< 30 years of age.

Time frame
1.5 years
2

Secondary Outcome #2

Quantify disease response, using end of Induction minimal residual disease (MRD) results, where an MRD value \< 0.01 is considered "negative."

Time frame
1.5 years
3

Secondary Outcome #3

Calculate incidence of nonalcoholic fatty liver disease (NAFLD), using ultrasound elastography, in pediatric and AYA patients newly diagnosed with ALL.

Time frame
1.5 years
4

Secondary Outcome #4

Calculate proportion of patients who experience other known toxicities of asparaginase treatment, as measured by CTCAE version 5.0 grade ≥ 3 hyper/hypoglycemia, hypertriglyceridemia, pancreatitis, and thrombosis.

Time frame
1.5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Hospital of Orange County

Lead sponsor

University of California, Irvine

Collaborator

Source ClinicalTrials.gov
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