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NCT05602194

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

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

440 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-24

Study Completion Date

2028-12-30

Brief Summary

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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.

Detailed Description

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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) 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 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).

Conditions

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B Acute Lymphoblastic Leukemia B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 B Acute Lymphoblastic Leukemia, BCR-ABL1-Like Lymphoblastic Lymphoma Mixed Phenotype Acute Leukemia T Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel with the option to cross over to Arm C to begin levocarnitine rescue

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Arm A (levocarnitine, standard of care chemotherapy)

Patients receive levocarnitine PO 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Calaspargase Pegol

Intervention Type DRUG

Given standard of care calaspargase pegol

Levocarnitine

Intervention Type DIETARY_SUPPLEMENT

Given PO or IV

Pegaspargase

Intervention Type DRUG

Given standard of care pegaspargase

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Calaspargase Pegol

Intervention Type DRUG

Given standard of care calaspargase pegol

Pegaspargase

Intervention Type DRUG

Given standard of care pegaspargase

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Arm C (rescue levocarnitine)

Patients in Arms A and B who develop conjugated hyperbilirubinemia \> 3 mg/dL during induction may receive levocarnitine rescue PO 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).

Group Type EXPERIMENTAL

Levocarnitine

Intervention Type DIETARY_SUPPLEMENT

Given PO or IV

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Calaspargase Pegol

Given standard of care calaspargase pegol

Intervention Type DRUG

Levocarnitine

Given PO or IV

Intervention Type DIETARY_SUPPLEMENT

Pegaspargase

Given standard of care pegaspargase

Intervention Type DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl) Asparlas Calaspargase Pegol-mknl EZN-2285 SC-PEG E. Coli L-Asparaginase Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase Carnitor L-carnitine 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 Quality of Life Assessment

Eligibility Criteria

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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):

* 1\. 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
* 2\. 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

Minimum Eligible Age

15 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Etan Orgel

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status RECRUITING

Kingman Regional Medical Center

Kingman, Arizona, United States

Site Status RECRUITING

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

Kaiser Permanente-Anaheim

Anaheim, California, United States

Site Status RECRUITING

PCR Oncology

Arroyo Grande, California, United States

Site Status RECRUITING

Kaiser Permanente-Bellflower

Bellflower, California, United States

Site Status RECRUITING

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status RECRUITING

Kaiser Permanente-Fontana

Fontana, California, United States

Site Status RECRUITING

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status RECRUITING

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Valley Children's Hospital

Madera, California, United States

Site Status RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status RECRUITING

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status RECRUITING

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status RECRUITING

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Kaiser Permanente-San Diego Mission

San Diego, California, United States

Site Status RECRUITING

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Site Status RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status RECRUITING

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status RECRUITING

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Site Status RECRUITING

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status RECRUITING

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status RECRUITING

Miami Cancer Institute

Miami, Florida, United States

Site Status RECRUITING

AdventHealth Orlando

Orlando, Florida, United States

Site Status RECRUITING

Nemours Children's Hospital

Orlando, Florida, United States

Site Status RECRUITING

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status RECRUITING

Sacred Heart Hospital

Pensacola, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status RECRUITING

Tampa General Hospital

Tampa, Florida, United States

Site Status RECRUITING

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status RECRUITING

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status RECRUITING

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Site Status RECRUITING

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Site Status RECRUITING

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Site Status RECRUITING

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

University of Illinois

Chicago, Illinois, United States

Site Status RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status RECRUITING

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, United States

Site Status RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status RECRUITING

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status RECRUITING

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status RECRUITING

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status RECRUITING

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status RECRUITING

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status RECRUITING

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status RECRUITING

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Bronson Battle Creek

Battle Creek, Michigan, United States

Site Status RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status RECRUITING

Michigan State University

East Lansing, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status RECRUITING

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status RECRUITING

Beacon Kalamazoo Cancer Center

Kalamazoo, Michigan, United States

Site Status RECRUITING

Beacon Kalamazoo

Kalamazoo, Michigan, United States

Site Status RECRUITING

Trinity Health Muskegon Hospital

Muskegon, Michigan, United States

Site Status RECRUITING

Corewell Health Lakeland Hospitals - Niles Hospital

Niles, Michigan, United States

Site Status RECRUITING

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, United States

Site Status RECRUITING

Corewell Health Reed City Hospital

Reed City, Michigan, United States

Site Status RECRUITING

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Site Status RECRUITING

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Saint Joseph, Michigan, United States

Site Status RECRUITING

Munson Medical Center

Traverse City, Michigan, United States

Site Status RECRUITING

University of Michigan Health - West

Wyoming, Michigan, United States

Site Status RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status RECRUITING

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status RECRUITING

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status RECRUITING

Carson Tahoe Regional Medical Center

Carson City, Nevada, United States

Site Status RECRUITING

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, United States

Site Status RECRUITING

Comprehensive Cancer Centers of Nevada-Horizon Ridge

Henderson, Nevada, United States

Site Status RECRUITING

OptumCare Cancer Care at Seven Hills

Henderson, Nevada, United States

Site Status RECRUITING

Comprehensive Cancer Centers of Nevada-Southeast Henderson

Henderson, Nevada, United States

Site Status RECRUITING

Las Vegas Urology - Green Valley

Henderson, Nevada, United States

Site Status RECRUITING

Las Vegas Urology - Pebble

Henderson, Nevada, United States

Site Status RECRUITING

Oncology Las Vegas - Henderson

Henderson, Nevada, United States

Site Status RECRUITING