NCT05602194|Active Not RecruitingPhase 3DMCFDA Drug

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

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

Children's Oncology Group ClinicalTrials.gov

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5 other identifiers

ACCL1931NCI-2022-08058COG-ACCL1931U24CA196173UG1CA189955

Study Type

interventional

Target

440

Locations

2 countries

Sites

228

Timeline

RegisteredNov 2022

StartedAug 2023

CompletionDec 2028

Brief Summary

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.

Trial Health

On Track

Trial Health Score

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

Enrollment

440

participants targeted

Target at P50-P75 for phase_3

Timeline

30mo left

Started Aug 2023

Longer than P75 for phase_3

Geographic Reach

2 countries

228 active sites

Status

active not 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

5.4 years study duration

Study Progress55%

Aug 2023Dec 2028

First Submitted

Initial submission to the registry

October 18, 2022

Completed

15 days until next milestone

First Posted

Study publicly available on registry

November 2, 2022

Completed

10 months until next milestone

Study Start

First participant enrolled

August 14, 2023

Completed

3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2026

Expected

2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2028

Last Updated

July 9, 2026

Status Verified

July 1, 2026

Enrollment Period

3.1 years

First QC Date

October 18, 2022

Last Update Submit

July 8, 2026

Conditions

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

Outcome Measures

Primary Outcomes (1)

Incidence of conjugated hyperbilirubinemia > 3 mg/dL during induction therapy
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 Outcomes (2)

Incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction therapy
During induction therapy (up-to 35-days after initiating induction chemotherapy)
Incidence of minimal residual disease (MRD) positivity (MRD >= 0.01%)
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)

Other Outcomes (17)

Incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 4 adverse events during induction chemotherapy
Up to 35 days (induction phase)
Incidence of daunorubicin, vincristine, and/or asparaginase chemotherapy dose reductions during induction chemotherapy
Up to 35 days (induction phase)
Percentage of planned dose given for daunorubicin, vincristine, and/or asparaginase during induction chemotherapy
Up to 35 days (induction phase)
+14 more other outcomes

Study Arms (3)

Arm A (levocarnitine, standard of care chemotherapy)

EXPERIMENTAL

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.

Procedure: Biospecimen CollectionDrug: Calaspargase PegolDietary Supplement: LevocarnitineDrug: PegaspargaseOther: Quality-of-Life Assessment

Arm B (standard of care chemotherapy)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen CollectionDrug: Calaspargase PegolDrug: PegaspargaseOther: Quality-of-Life Assessment

Arm C (rescue levocarnitine)

EXPERIMENTAL

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

Interventions

PegaspargaseDRUG

Given standard of care pegaspargase

Also known as: 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

Arm A (levocarnitine, standard of care chemotherapy)Arm B (standard of care chemotherapy)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (levocarnitine, standard of care chemotherapy)Arm B (standard of care chemotherapy)

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (levocarnitine, standard of care chemotherapy)Arm B (standard of care chemotherapy)

Calaspargase PegolDRUG

Given standard of care calaspargase pegol

Also known as: 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

Arm A (levocarnitine, standard of care chemotherapy)Arm B (standard of care chemotherapy)

LevocarnitineDIETARY_SUPPLEMENT

Given PO or IV

Also known as: Carnitor, L-carnitine

Arm A (levocarnitine, standard of care chemotherapy)Arm C (rescue levocarnitine)

Eligibility Criteria

Age15 Years - 40 Years

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

\>= 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)
+8 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Children's Oncology Grouplead

Study Sites (228)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Kingman Regional Medical Center

Kingman, Arizona, 86401, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Kaiser Permanente-Anaheim

Anaheim, California, 92806, United States

Location

PCR Oncology

Arroyo Grande, California, 93420, United States

Location

Kaiser Permanente-Bellflower

Bellflower, California, 90706, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Kaiser Permanente-Fontana

Fontana, California, 92335, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Kaiser Permanente-San Diego Mission

San Diego, California, 92108, United States

Location

Kaiser Permanente-San Diego Zion

San Diego, California, 92120, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

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

Denver, Colorado, 80218, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

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

Tampa, Florida, 33607, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States

Location

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, 83619, United States

Location

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, 83642, United States

Location

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, 83687, United States

Location

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, 83301, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

Location

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, 60068, United States

Location

OSF Children's Hospital of Illinois

Peoria, Illinois, 61637, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Bronson Battle Creek

Battle Creek, Michigan, 49017, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Michigan State University

East Lansing, Michigan, 48823, United States

Location

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

Location

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

Grand Rapids, Michigan, 49503, United States

Location

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, 49503, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Beacon Kalamazoo Cancer Center

Kalamazoo, Michigan, 49009, United States

Location

Beacon Kalamazoo

Kalamazoo, Michigan, 49048, United States

Location

Trinity Health Muskegon Hospital

Muskegon, Michigan, 49444, United States

Location

Corewell Health Lakeland Hospitals - Niles Hospital

Niles, Michigan, 49120, United States

Location

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, 49444, United States

Location

Corewell Health Reed City Hospital

Reed City, Michigan, 49677, United States

Location

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085, United States

Location

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

University of Michigan Health - West

Wyoming, Michigan, 49519, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Carson Tahoe Regional Medical Center

Carson City, Nevada, 89703, United States

Location

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, 89052, United States

Location

Comprehensive Cancer Centers of Nevada-Horizon Ridge

Henderson, Nevada, 89052, United States

Location

Comprehensive Cancer Centers of Nevada-Southeast Henderson

Henderson, Nevada, 89074, United States

Location

Las Vegas Urology - Green Valley

Henderson, Nevada, 89074, United States

Location

Las Vegas Urology - Pebble

Henderson, Nevada, 89074, United States

Location

Oncology Las Vegas - Henderson

Henderson, Nevada, 89074, United States

Location

Urology Specialists of Nevada - Green Valley

Henderson, Nevada, 89074, United States

Location

Las Vegas Urology - Pecos

Las Vegas, Nevada, 89074, United States

Location

OptumCare Cancer Care at Charleston

Las Vegas, Nevada, 89102, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Hope Cancer Care of Nevada

Las Vegas, Nevada, 89103, United States

Location

Radiation Oncology Centers of Nevada Central

Las Vegas, Nevada, 89106, United States

Location

Urology Specialists of Nevada - Central

Las Vegas, Nevada, 89106, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States

Location

Las Vegas Urology - Sunset

Las Vegas, Nevada, 89113, United States

Location

Urology Specialists of Nevada - Southwest

Las Vegas, Nevada, 89113, United States

Location

Radiation Oncology Centers of Nevada Southeast

Las Vegas, Nevada, 89119, United States

Location

Ann M Wierman MD LTD