NCT05501899

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Mar 2023

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 12, 2022

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 16, 2022

Completed
7 months until next milestone

Study Start

First participant enrolled

March 3, 2023

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

August 21, 2024

Status Verified

August 1, 2024

Enrollment Period

1.8 years

First QC Date

August 12, 2022

Last Update Submit

August 20, 2024

Conditions

Acute Lymphoblastic LeukemiaHepatotoxicity

Outcome Measures

Primary Outcomes (2)

  • 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.

    1.5 years

  • 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.

    1.5 years

Secondary Outcomes (4)

  • Secondary Outcome #1

    1.5 years

  • Secondary Outcome #2

    1.5 years

  • Secondary Outcome #3

    1.5 years

  • Secondary Outcome #4

    1.5 years

Study Arms (1)

Treatment Arm (single arm)

EXPERIMENTAL
Drug: Levocarnitine

Interventions

LevocarnitineDRUG

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)

Also known as: Carnitor®
Treatment Arm (single arm)

Eligibility Criteria

Age5 Years - 29 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Related Publications (12)

  • Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.

    PMID: 22412151BACKGROUND

  • Kadan-Lottick NS, Ness KK, Bhatia S, Gurney JG. Survival variability by race and ethnicity in childhood acute lymphoblastic leukemia. JAMA. 2003 Oct 15;290(15):2008-14. doi: 10.1001/jama.290.15.2008.

    PMID: 14559954BACKGROUND

  • DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, Amrein PC, Ballen KK, Seftel MD, Turner AR, Leber B, Howson-Jan K, Kelly K, Cohen S, Matthews JH, Savoie L, Wadleigh M, Sirulnik LA, Galinsky I, Neuberg DS, Sallan SE, Stone RM. Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015 Mar;29(3):526-34. doi: 10.1038/leu.2014.229. Epub 2014 Jul 31.

    PMID: 25079173BACKGROUND

  • Stock W, Luger SM, Advani AS, Yin J, Harvey RC, Mullighan CG, Willman CL, Fulton N, Laumann KM, Malnassy G, Paietta E, Parker E, Geyer S, Mrozek K, Bloomfield CD, Sanford B, Marcucci G, Liedtke M, Claxton DF, Foster MC, Bogart JA, Grecula JC, Appelbaum FR, Erba H, Litzow MR, Tallman MS, Stone RM, Larson RA. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019 Apr 4;133(14):1548-1559. doi: 10.1182/blood-2018-10-881961. Epub 2019 Jan 18.

    PMID: 30658992BACKGROUND

  • Aldoss I, Douer D, Behrendt CE, Chaudhary P, Mohrbacher A, Vrona J, Pullarkat V. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia. Eur J Haematol. 2016 Apr;96(4):375-80. doi: 10.1111/ejh.12600. Epub 2015 Jun 25.

    PMID: 26095294BACKGROUND

  • Raetz EA, Salzer WL. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010 Oct;32(7):554-63. doi: 10.1097/MPH.0b013e3181e6f003.

    PMID: 20724951BACKGROUND

  • Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014 Feb 26;311(8):806-14. doi: 10.1001/jama.2014.732.

    PMID: 24570244BACKGROUND

  • van der Sluis IM, Vrooman LM, Pieters R, Baruchel A, Escherich G, Goulden N, Mondelaers V, Sanchez de Toledo J, Rizzari C, Silverman LB, Whitlock JA. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016 Mar;101(3):279-85. doi: 10.3324/haematol.2015.137380.

    PMID: 26928249BACKGROUND

  • Romano M, Vacante M, Cristaldi E, Colonna V, Gargante MP, Cammalleri L, Malaguarnera M. L-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha-interferon and ribavirin. Dig Dis Sci. 2008 Apr;53(4):1114-21. doi: 10.1007/s10620-007-9983-1. Epub 2007 Oct 16.

    PMID: 17939042BACKGROUND

  • Schulte RR, Madiwale MV, Flower A, Hochberg J, Burke MJ, McNeer JL, DuVall A, Bleyer A. Levocarnitine for asparaginase-induced hepatic injury: a multi-institutional case series and review of the literature. Leuk Lymphoma. 2018 Oct;59(10):2360-2368. doi: 10.1080/10428194.2018.1435873. Epub 2018 Feb 12.

    PMID: 29431566BACKGROUND

  • Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020 Mar 26;135(13):987-995. doi: 10.1182/blood.2019002477.

    PMID: 31977001BACKGROUND

  • Schulte R, Hinson A, Huynh V, Breese EH, Pierro J, Rotz S, Mixon BA, McNeer JL, Burke MJ, Orgel E. Levocarnitine for pegaspargase-induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia. Cancer Med. 2021 Nov;10(21):7551-7560. doi: 10.1002/cam4.4281. Epub 2021 Sep 16.

    PMID: 34528411BACKGROUND

Related Links

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Carnitine

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium CompoundsQuaternary Ammonium CompoundsAminesOrganic Chemicals

Central Study Contacts

Van T. Huynh, M.D.

CONTACT

(714) 509-4348vahuynh@choc.org

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 12, 2022

First Posted

August 16, 2022

Study Start

March 3, 2023

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

August 21, 2024

Record last verified: 2024-08

Data Sharing

IPD Sharing
Will not share

Locations

US(2)