Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT05501899|
Recruitment Status : Not yet recruiting
First Posted : August 16, 2022
Last Update Posted : August 16, 2022
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Hepatotoxicity||Drug: Levocarnitine||Early Phase 1|
- Prospectively evaluate whether the prophylactic use of levocarnitine during Induction and Consolidation (phases with asparaginase therapy) in ALL patients receiving treatment according to a Children's Oncology Group (COG) treatment protocol reduces hepatotoxicity.
- Demonstrate an association between ethnicity and liver function test abnormalities in children and AYAs with ALL. Specifically, that Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥ 3 elevated liver function tests is more prevalent in self-identified Latinos as compared to other ethnicities in a retrospective control group.
- Determine whether obesity or overweight status, as measured by body mass index, at diagnosis increases the risk of hepatic dysfunction.
- Quantify the disease response, based on the end of Induction minimal residual disease (MRD) in the bone marrow of patients receiving levocarnitine, compared to historical controls to determine that levocarnitine does not have a negative impact on MRD.
- Assess incidence of nonalcoholic fatty liver disease (NAFLD), via non-invasive ultrasound elastography, in pediatric and AYA patients newly diagnosed with ALL.
- Assess incidence of other known toxicities of asparaginase treatment, including hyper/hypoglycemia, hypertriglyceridemia, pancreatitis, and thrombosis that are CTCAE version 5.0 grade ≥ 3 with onset ≤ 30 days (or next dose if sooner) of asparaginase.
The proposal is a non-randomized case-control pilot study that will use retrospective case-control data as comparison (i.e., control group).
A sample of 20 pediatric and AYA patients, ages 5 to < 30 years, newly diagnosed with ALL will be enrolled to study. Participants who withdraw or who are withdrawn from study, who have taken less than 50% of planned levocarnitine supplementation, and who did not have a post-levocarnitine supplementation laboratory testing will be replaced. An additional 20 retrospective cases -- matched by age at diagnosis, biological sex, and risk classification at initial diagnosis -- will be included to provide control data.
Levocarnitine will be administered by mouth twice daily during Induction and Consolidation phases of treatment for patients with ALL who are treated as per a COG treatment plan (either on study or treated according to the protocol). The duration of intervention is expected to be approximately three months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia|
|Estimated Study Start Date :||September 1, 2022|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
|Experimental: Treatment Arm (single arm)||
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)
Other Name: Carnitor®
- Primary Outcome #1 [ Time Frame: 1.5 years ]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.
- Primary Outcome #2 [ Time Frame: 1.5 years ]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.
- Secondary Outcome #1 [ Time Frame: 1.5 years ]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.
- Secondary Outcome #2 [ Time Frame: 1.5 years ]Quantify disease response, using end of Induction minimal residual disease (MRD) results, where an MRD value < 0.01 is considered "negative."
- Secondary Outcome #3 [ Time Frame: 1.5 years ]Calculate incidence of nonalcoholic fatty liver disease (NAFLD), using ultrasound elastography, in pediatric and AYA patients newly diagnosed with ALL.
- Secondary Outcome #4 [ Time Frame: 1.5 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05501899
|Contact: Van T. Huynh, M.D.||(714) firstname.lastname@example.org|
|United States, California|
|Chao Family Comprehensive Cancer Center, University of California, Irvine|
|Orange, California, United States, 92868|
|Contact: Deepa Jeyakumar, MD 714-456-5153 email@example.com|
|Children's Hospital of Orange County|
|Orange, California, United States, 92868|