Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma

May 29, 2026 updated by: Children's Oncology Group

A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy

This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. Asparaginase is part of the standard of care chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often prevents delivery of planned chemotherapy, thereby potentially compromising outcomes. Some groups of people may also be at higher risk for liver damage due to the presence of fat in the liver even before starting chemotherapy. Patients who are of Japanese descent, Native Hawaiian, Hispanic or Latinx may be at greater risk for liver damage from chemotherapy for this reason. Carnitine is a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is necessary for metabolism and its deficiency or absence is associated with liver and other organ damage. Levocarnitine is a drug used to provide extra carnitine. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase. The overall goal of this study is to determine whether adding levocarnitine to standard of care chemotherapy will reduce the chance of developing severe liver damage from asparaginase chemotherapy in ALL, LL and/or MPAL patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine in a randomized manner whether the addition of levocarnitine prophylaxis to asparaginase-containing regimens will decrease the incidence of conjugated hyperbilirubinemia (> 3 mg/dL) during ALL induction therapy for adolescents and young adults (adolescents and young adults [AYAs], age 15-39 years).

SECONDARY OBJECTIVES:

I. To examine the impact of levocarnitine prophylaxis on differences in the incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during ALL induction.

II. To compare rates of minimal residual disease (MRD) positivity at end of induction and describe MRD+ by end of consolidation (EOC) in those receiving ALL induction chemotherapy with and without levocarnitine.

EXPLORATORY OBJECTIVES:

I. To compare rates of toxicity and associated dose reductions for chemotherapy administered with and without concomitant levocarnitine supplementation.

II. To compare across study arms the peak levels during induction of conjugated and total bilirubin, AST, ALT, and duration of conjugated hyperbilirubinemia from onset > 3 mg/dL to =< 3 mg/dL.

III. To describe the efficacy of levocarnitine prophylaxis to reduce the incidence and/or severity of early patient-reported chemotherapy-induced peripheral neuropathy.

IV. To describe the three-year event-free and overall survival (EFS/OS) in those treated with and without levocarnitine prophylaxis.

V. To examine the association of age with asparaginase activity and asparaginase-associated hepatotoxicity during induction.

VI. To examine the association of body-mass-index (BMI) percentile (or absolute BMI for young adults) with asparaginase activity and asparaginase-associated hepatotoxicity during induction.

VII. To describe adherence by self-report and pill-count to oral levocarnitine in patients randomized to the intervention arm.

VIII. To examine the association of plasma levels of carnitine and related markers with the efficacy of levocarnitine supplementation.

IX. To determine the impact of inherited genetic variation on hepatoxicity and levocarnitine efficacy.

OUTLINE: Patients are randomized to 1 of 2 arms (arm A vs. B).

ARM A: Patients receive levocarnitine orally (PO) three times daily (TID) or intravenously (IV) as a bolus over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) starting prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol and continued through the earlier of the last day of Induction phase (i.e., day prior to start of next phase) or Induction day 35. Patients may also undergo blood sample collection during screening and on study.

ARM B: Patients receive standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.

ARM C (RESCUE): Patients in Arms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO TID or IV as a bolus dose over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).

Study Type

Interventional

Enrollment (Estimated)

440

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Children's Hospital
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Kingman, Arizona, United States, 86401
        • Kingman Regional Medical Center
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Arroyo Grande, California, United States, 93420
        • PCR Oncology
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Fontana, California, United States, 92335
        • Kaiser Permanente-Fontana
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's and Women's Hospital Long Beach
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital Oakland
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92120
        • Kaiser Permanente-San Diego Zion
      • San Diego, California, United States, 92108
        • Kaiser Permanente-San Diego Mission
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Gainesville, Florida, United States, 32610
        • UF Health Cancer Institute - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Hospital
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • St. Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Children's Healthcare of Atlanta - Arthur M Blank Hospital
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, United States, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83687
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Children's Hospital-Oak Lawn
      • Park Ridge, Illinois, United States, 60068
        • Advocate Children's Hospital-Park Ridge
      • Peoria, Illinois, United States, 61637
        • OSF Children's Hospital of Illinois
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
      • East Lansing, Michigan, United States, 48823
        • Michigan State University
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49009
        • Beacon Kalamazoo Cancer Center
      • Kalamazoo, Michigan, United States, 49048
        • Beacon Kalamazoo
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Niles, Michigan, United States, 49120
        • Corewell Health Lakeland Hospitals - Niles Hospital
      • Norton Shores, Michigan, United States, 49444
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Reed City, Michigan, United States, 49677
        • Corewell Health Reed City Hospital
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Wyoming, Michigan, United States, 49519
        • University of Michigan Health - West
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Carson Tahoe Regional Medical Center
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada - Henderson
      • Henderson, Nevada, United States, 89074
        • Comprehensive Cancer Centers of Nevada-Southeast Henderson
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada-Horizon Ridge
      • Henderson, Nevada, United States, 89074
        • Las Vegas Urology - Green Valley
      • Henderson, Nevada, United States, 89074
        • Las Vegas Urology - Pebble
      • Henderson, Nevada, United States, 89074
        • Urology Specialists of Nevada - Green Valley
      • Henderson, Nevada, United States, 89074
        • Oncology Las Vegas - Henderson
      • Las Vegas, Nevada, United States, 89144
        • Summerlin Hospital Medical Center
      • Las Vegas, Nevada, United States, 89109
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, United States, 89102
        • OptumCare Cancer Care at Charleston
      • Las Vegas, Nevada, United States, 89106
        • Radiation Oncology Centers of Nevada Central
      • Las Vegas, Nevada, United States, 89119
        • Radiation Oncology Centers of Nevada Southeast
      • Las Vegas, Nevada, United States, 89128
        • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas, Nevada, United States, 89128
        • OptumCare Cancer Care at MountainView
      • Las Vegas, Nevada, United States, 89135
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89144
        • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas, Nevada, United States, 89144
        • Comprehensive Cancer Centers of Nevada-Summerlin
      • Las Vegas, Nevada, United States, 89148
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas, Nevada, United States, 89102
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, United States, 89128
        • Ann M Wierman MD LTD
      • Las Vegas, Nevada, United States, 89074
        • Las Vegas Urology - Pecos
      • Las Vegas, Nevada, United States, 89103
        • Hope Cancer Care of Nevada
      • Las Vegas, Nevada, United States, 89106
        • Urology Specialists of Nevada - Central
      • Las Vegas, Nevada, United States, 89113
        • Las Vegas Urology - Sunset
      • Las Vegas, Nevada, United States, 89128
        • Las Vegas Urology - Cathedral Rock
      • Las Vegas, Nevada, United States, 89128
        • Las Vegas Urology - Smoke Ranch
      • Las Vegas, Nevada, United States, 89128
        • Urology Specialists of Nevada - Northwest
      • Las Vegas, Nevada, United States, 89113
        • Urology Specialists of Nevada - Southwest
      • Las Vegas, Nevada, United States, 89128
        • Oncology Las Vegas - Tenaya
      • Las Vegas, Nevada, United States, 89183
        • OptumCare Cancer Care at Fort Apache
      • Pahrump, Nevada, United States, 89048
        • Hope Cancer Care of Nevada-Pahrump
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
      • Reno, Nevada, United States, 89503
        • Saint Mary's Regional Medical Center
      • Reno, Nevada, United States, 89509
        • Radiation Oncology Associates
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Neptune City, New Jersey, United States, 07753
        • Jersey Shore Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • Saint Joseph's Regional Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Presbyterian Hospital
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Brooklyn, New York, United States, 11219
        • Maimonides Medical Center
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital - Long Island
      • New Hyde Park, New York, United States, 11040
        • The Steven and Alexandra Cohen Children's Medical Center of New York
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • The Bronx, New York, United States, 10467
        • Children's Hospital at Montefiore
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at Saint Francis
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Greenville Memorial Hospital
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • El Paso, Texas, United States, 79905
        • El Paso Children's Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Lubbock, Texas, United States, 79410
        • Covenant Children's Hospital
      • Lubbock, Texas, United States, 79415
        • UMC Cancer Center / UMC Health System
      • McAllen, Texas, United States, 78503
        • Vannie Cook Children's Clinic
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78207
        • Children's Hospital of San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
      • Roanoke, Virginia, United States, 24014
        • Carilion Children's
    • Washington
      • Renton, Washington, United States, 98055
        • Valley Medical Center
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Hospital and Health Center
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
      • Yakima, Washington, United States, 98902
        • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Wisconsin
      • Burlington, Wisconsin, United States, 53105
        • Aurora Cancer Care-Southern Lakes VLCC
      • Cudahy, Wisconsin, United States, 53110
        • Aurora Saint Luke's South Shore
      • Germantown, Wisconsin, United States, 53022
        • Aurora Health Care Germantown Health Center
      • Grafton, Wisconsin, United States, 53024
        • Aurora Cancer Care-Grafton
      • Green Bay, Wisconsin, United States, 54311
        • Aurora BayCare Medical Center
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53209
        • Aurora Cancer Care-Milwaukee
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • Milwaukee, Wisconsin, United States, 53233
        • Aurora Sinai Medical Center
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin
      • Oshkosh, Wisconsin, United States, 54904
        • Vince Lombardi Cancer Clinic - Oshkosh
      • Racine, Wisconsin, United States, 53406
        • Aurora Cancer Care-Racine
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Two Rivers, Wisconsin, United States, 54241
        • Vince Lombardi Cancer Clinic-Two Rivers
      • Wauwatosa, Wisconsin, United States, 53226
        • Aurora Cancer Care-Milwaukee West
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • >= 15 and < 40 years at time of diagnosis

  • Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL)

    • Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use of tyrosine kinase inhibitors [TKI] or CRLF2- targeted concomitant medication must be documented, if used)
  • Conjugated bilirubin =< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment), and

  • Serum glutamate pyruvate transaminase (SGPT) (ALT) =< 225 U/L (=< 5x ULN) (within 7 days prior to enrollment), and

    • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50 U/L regardless of baseline

  • SGOT (AST) =< 250 U/L (=< 5x ULN) (within 7 days prior to enrollment)

    • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline
  • For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days

  • PEDIATRIC PATIENTS (AGE 15-17 years):

    • A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR

    • A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment):

      • Estimated GFR (eGFR) >= 30 mL/min/1.73 m^2.

        • An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorped
      • Measured GFR >= 30 mL/min/1.73 m^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard)

  • ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight

    • An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc
  • Berlin-Frankfurt-Munich (BFM), Children's Oncology Group (COG), or C10403-based Induction regimen and must be inclusive of >= 1 dose of pegaspargase or calaspargase pegol, and
  • First dose of asparaginase must be planned within the first week of induction therapy, and

  • Dose of pegaspargase or calaspargase pegol must be >= 1,000 IU/ m^2 (dose-capping permitted per primary regimen)

    • Note: Co-enrollment on a therapeutic consortia trial is not required
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • 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)
  • Unable to tolerate oral formulation of study drug at enrollment

  • Patients who received chemotherapy or treatment for a prior malignancy are not eligible

    • The following are permitted: steroid prophase, hydroxyurea, or other cytoreduction prior to initiation of Induction chemotherapy (must be documented) and chemotherapy for current diagnosis (i.e. initiation of Induction therapy within enrollment window). Chemotherapy prior to enrollment for treatment of a non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also permitted and must be documented
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm B (standard of care chemotherapy)
Patients receive standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Drug: Pegaspargase
Given standard of care pegaspargase
Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
Drug: Calaspargase Pegol
Given standard of care calaspargase pegol
Other Names:
  • Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
  • Asparlas
  • EZN-2285
  • SC-PEG E. Coli L-Asparaginase
  • Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
  • Calaspargase Pegol-mknl
Experimental: Arm A (levocarnitine, standard of care chemotherapy)
Patients receive levocarnitine PO TID or IV as a bolus over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) starting prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol and continued through the earlier of the last day of Induction phase (i.e., day prior to start of next phase) or Induction day 35. Patients may also undergo blood sample collection during screening and on study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Dietary supplement: Levocarnitine
Given PO or IV
Other Names:
  • L-carnitine
  • Carnitor
Drug: Pegaspargase
Given standard of care pegaspargase
Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
Drug: Calaspargase Pegol
Given standard of care calaspargase pegol
Other Names:
  • Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
  • Asparlas
  • EZN-2285
  • SC-PEG E. Coli L-Asparaginase
  • Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
  • Calaspargase Pegol-mknl
Experimental: Arm C (rescue levocarnitine)
Patients in Arms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO TID or IV as a bolus dose over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).
Dietary supplement: Levocarnitine
Given PO or IV
Other Names:
  • L-carnitine
  • Carnitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of conjugated hyperbilirubinemia > 3 mg/dL during induction therapy
Time Frame: During induction therapy (up-to 35-days after initiating induction chemotherapy)
For patients assigned to arms A and B, the investigators will separately estimate the proportion of patients who experience conjugated hyperbilirubinemia > 3mg/dL during induction chemotherapy by arm along with corresponding 95% confidence intervals.
During induction therapy (up-to 35-days after initiating induction chemotherapy)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of minimal residual disease (MRD) positivity (MRD >= 0.01%)
Time Frame: At end of induction chemotherapy (up-to 35-days after initiating induction chemotherapy), and at end of consolidation chemotherapy (up-to day 56 days after initiating induction chemotherapy)
For patients assigned to arms A and B, the proportion having MRD positivity at the end of induction chemotherapy will be estimated separately by arm along with corresponding 95% confidence intervals. For patients assigned to arms A and B, the proportion having MRD positivity at the end of consolidation chemotherapy will be estimated separately by arm along with corresponding 95% confidence intervals (only patients with end of consolidation MRD evaluated and who did not get placed on the rescue arm C will be included).
At end of induction chemotherapy (up-to 35-days after initiating induction chemotherapy), and at end of consolidation chemotherapy (up-to day 56 days after initiating induction chemotherapy)
Incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction therapy
Time Frame: During induction therapy (up-to 35-days after initiating induction chemotherapy)
For patients assigned to arms A and B, the investigators will separately estimate the proportion of patients who experience grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction chemotherapy by arm along with corresponding 95% confidence intervals.
During induction therapy (up-to 35-days after initiating induction chemotherapy)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of planned dose given for daunorubicin, vincristine, and/or asparaginase during induction chemotherapy
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and b, the median percent planned dose given during induction will also be calculated as well as 95% confidence intervals.
Up to 35 days (induction phase)
Peak levels during induction of conjugated bilirubin
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the investigators will calculate median peak conjugated bilirubin as well as corresponding 95% confidence intervals.
Up to 35 days (induction phase)
Peak levels of ALT during induction chemotherapy
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
Up to 35 days (induction phase)
Severity of patient-reported chemotherapy induced peripheral neuropathy (CIPN) as measured by the 11-question Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) survey
Time Frame: Up to 35 days (induction phase)
The 11-question FACT/GOG-NTX survey will be used to assess patient reported CIPN, where a higher score indicates more severe CIPN. For patients on arms A and B, a median and corresponding 95% confidence interval will be estimated and reported.
Up to 35 days (induction phase)
Overall survival (OS)
Time Frame: Time from study entry to death or date of last contact for those alive at last contact, assessed up to 3 years
For OS analysis, 3-year OS probabilities and corresponding 95% CI will be estimated for Arms A and B, separately, using the Kaplan Meier method.
Time from study entry to death or date of last contact for those alive at last contact, assessed up to 3 years
Asparaginase activity
Time Frame: Days 8, 15, and 22
Spearman's correlation coefficients and corresponding 95% confidence intervals will be reported comparing asparaginase activity to age and BMI.
Days 8, 15, and 22
Adherence to oral levocarnitine measured by percentage dose compliance (% doses reported taken relative to prescribed)
Time Frame: Up to 35 days (induction phase)
The investigators will report the median percentage dose compliance across patients assigned to arm A as well as a 95% confidence interval.
Up to 35 days (induction phase)
Incidence of daunorubicin, vincristine, and/or asparaginase chemotherapy dose reductions during induction chemotherapy
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the proportion receiving a dose reduction during induction chemotherapy relative to planned doses at the beginning of induction chemotherapy for daunorubicin, vincristine, and/or asparaginase will be estimated along with 95% confidence intervals
Up to 35 days (induction phase)
Peak levels during induction of total bilirubin
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
Up to 35 days (induction phase)
Peak levels of AST during induction chemotherapy
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
Up to 35 days (induction phase)
Association of body-mass-index (BMI) percentile (or absolute BMI for young adults) with asparaginase activity and asparaginase-associated hepatotoxicity during induction therapy
Time Frame: Days 8, 15, and 22
The association of BMI percentile with asparaginase activity will be assessed using Spearman's correlation. Logistic regression will be used to separately assess the relationship of BMI (considered as a continuous variable and an ordinal variable) and asparaginase activity with hepatotoxicity (conjugated hyperbilirubinemia, ALT) dichotomized as conjugated hyperbilirubinemia >3 versus =< 3 mg/dl and CTCAE grade >= 3 versus < 3 AST or ALT, respectively. Analyses will be performed separately for asparaginase activity measured on Days ~8, 15, and 22 and for Arms A and B.
Days 8, 15, and 22
Incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 4 adverse events during induction chemotherapy
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A and B, the proportion experiencing CTCAE grade >=4 adverse events by the end of induction chemotherapy will be estimated along with 95% confidence intervals.
Up to 35 days (induction phase)
Event free survival (EFS)
Time Frame: The time from randomization to first event (relapse, second malignant neoplasm, remission or death) or date of last contact for those who are disease-free, assessed up to 3 years
For EFS analysis, 3-year EFS probabilities and corresponding 95% confidence interval (CI) will be estimated for Arms A and B, separately, using the Kaplan Meier method. A log-rank test will be used to compare EFS between Arm A versus Arm B (Arm C patients will not contribute to this analysis after they start levocarnitine rescue). Additional EFS analyses comparing Arms A versus B will also be performed using Cox regression models adjusted for "levocarnitine rescue" (i.e., Arm C patients/time) as a time-varying covariate. Hazard ratio and the corresponding 95%CI will be reported for each arm.
The time from randomization to first event (relapse, second malignant neoplasm, remission or death) or date of last contact for those who are disease-free, assessed up to 3 years
Days of conjugated hyperbilirubinemia (> 3 mg/dL) to =< 3 mg/dL during induction
Time Frame: Up to 35 days (induction phase)
For patients assigned to arms A, B, and C, the investigators will calculate the median days from onset of conjugated hyperbilirubinemia as well as 95% confidence intervals.
Up to 35 days (induction phase)
Adherence to oral levocarnitine during induction chemotherapy measured by percentage of pills returned relative to those prescribed
Time Frame: Up to 35 days (induction phase)
Descriptive statistics (mean [standard deviation (sd)] or median (range) as appropriate) will be used to summarize adherence to levocarnitine tablets during induction in AYA patients randomized to the intervention Arm A as assessed by self-report (% doses compliant) and pill-counts (% pills returned). The percentage of doses compliant will be calculated as: the number of reported missed doses / total prescribed doses for the entire induction period. And the percentage of pills returned will be calculated as the number of pills returned / (number of pills dispensed - number of pills prescribed not taken [i.e., for prescribed dose reductions for toxicity for the entire induction period]).
Up to 35 days (induction phase)
Mean plasma levels of carnitine
Time Frame: Up to 3 years
The Investigators will calculate mean plasma levels of carnitine at baseline and at steady state for patients in arms A and B who do and do not experience conjugated hyperbilirubinemia > 3 mg/dL and will calculate corresponding 95% confidence intervals.
Up to 3 years
Impact inherited genetic variation on hepatoxicity and levocarnitine efficacy
Time Frame: Up to 3 years
This aim will use specimens banked for future research to describe the association of candidate genes (PNPLA3, SOD2, GST family, other) with conjugated hyperbilirubinemia > 3 mg/dL and CTCAE Grade ≥ 3 AST or ALT elevations between treatment arms. Analyses will include ethnic and racial differences, with ancestry determined by self-report and complementary admixture mapping. The association of observed genetic differences with oxidant stress markers (e.g., protein oxidation, lipid peroxidation, total oxidant capacity) pre- and post-asparaginase will be assessed. In general, a multivariable logistic regression model will be used to examine the association between the occurrence of the primary endpoint and the genetic variant of interest, inclusive of covariates: age, obesity, and treatment versus control arm (1:1).
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Investigators

  • Principal Investigator: Etan Orgel, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 14, 2023

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

October 18, 2022

First Submitted That Met QC Criteria

October 28, 2022

First Posted (Actual)

November 2, 2022

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACCL1931 (Other Identifier: CTEP)
  • UG1CA189955 (U.S. NIH Grant/Contract)
  • U24CA196173 (U.S. NIH Grant/Contract)
  • NCI-2022-08058 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • COG-ACCL1931 (Other Identifier: DCP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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