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Trial Title:
Use of Levocarnitine to Reduce Asparaginase Hepatotoxicity in Patients With Acute Lymphoblastic Leukemia
NCT ID:
NCT05501899
Condition:
Acute Lymphoblastic Leukemia
Hepatotoxicity
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Supportive Care
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Levocarnitine
Description:
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)
Arm group label:
Treatment Arm (single arm)
Other name:
Carnitor®
Summary:
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.
Detailed description:
Primary Aims
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.
2. 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.
Secondary Aims
1. Determine whether obesity or overweight status, as measured by body mass index, at
diagnosis increases the risk of hepatic dysfunction.
2. 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.
3. Assess incidence of nonalcoholic fatty liver disease (NAFLD), via non-invasive
ultrasound elastography, in pediatric and AYA patients newly diagnosed with ALL.
4. 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.
Study Design:
The proposal is a non-randomized case-control pilot study that will use retrospective
case-control data as comparison (i.e., control group).
Participants:
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.
Study Intervention:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- Known allergic reaction to levocarnitine or its components
- Presence of severely compromised renal function or end-stage renal disease
- Pregnancy or lactation
- Warfarin therapy
- History of seizures prior to ALL diagnosis
- Known inborn error of metabolism
Gender:
All
Minimum age:
5 Years
Maximum age:
29 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chao Family Comprehensive Cancer Center, University of California, Irvine
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Deepa Jeyakumar, MD
Phone:
714-456-5153
Email:
djeyakum@uci.edu
Facility:
Name:
Children's Hospital of Orange County
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Van T. Huynh, M.D.
Phone:
714-509-4348
Email:
vahuynh@choc.org
Investigator:
Last name:
Van T. Huynh, M.D.
Email:
Principal Investigator
Start date:
March 3, 2023
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Children's Hospital of Orange County
Agency class:
Other
Collaborator:
Agency:
University of California, Irvine
Agency class:
Other
Source:
Children's Hospital of Orange County
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05501899
https://seer.cancer.gov/archive/csr/1975_2011/