Calaspargase Pegol: Given standard of care calaspargase pegol
Levocarnitine: Given PO or IV
Pegaspargase: Given standard of care pegaspargase
Quality-of-Life Assessment: Ancillary studies
Study 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.
Eligibility
Sex
ALL
Min age
15 Years
Max age
40 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Incidence of conjugated hyperbilirubinemia > 3 mg/dL during induction therapy — 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.
Trial sites (228)
Facility
City
Region
Status
Children's Hospital of Alabama
Birmingham
Alabama
Providence Alaska Medical Center
Anchorage
Alaska
Kingman Regional Medical Center
Kingman
Arizona
Phoenix Childrens Hospital
Phoenix
Arizona
Banner University Medical Center - Tucson
Tucson
Arizona
Arkansas Children's Hospital
Little Rock
Arkansas
Kaiser Permanente-Anaheim
Anaheim
California
PCR Oncology
Arroyo Grande
California
Kaiser Permanente-Bellflower
Bellflower
California
Kaiser Permanente Downey Medical Center
Downey
California
City of Hope Comprehensive Cancer Center
Duarte
California
Kaiser Permanente-Fontana
Fontana
California
Loma Linda University Medical Center
Loma Linda
California
Miller Children's and Women's Hospital Long Beach
Long Beach
California
Children's Hospital Los Angeles
Los Angeles
California
Kaiser Permanente Los Angeles Medical Center
Los Angeles
California
Valley Children's Hospital
Madera
California
UCSF Benioff Children's Hospital Oakland
Oakland
California
Lucile Packard Children's Hospital Stanford University
Palo Alto
California
Stanford Cancer Institute Palo Alto
Palo Alto
California
Sutter Medical Center Sacramento
Sacramento
California
University of California Davis Comprehensive Cancer Center
Sacramento
California
Kaiser Permanente-San Diego Mission
San Diego
California
Kaiser Permanente-San Diego Zion
San Diego
California
UCSF Medical Center-Mission Bay
San Francisco
California
Children's Hospital Colorado
Aurora
Colorado
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver
Colorado
Alfred I duPont Hospital for Children
Wilmington
Delaware
Children's National Medical Center
Washington D.C.
District of Columbia
Golisano Children's Hospital of Southwest Florida
Fort Myers
Florida
UF Health Cancer Institute - Gainesville
Gainesville
Florida
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood
Florida
Nemours Children's Clinic-Jacksonville
Jacksonville
Florida
Nicklaus Children's Hospital
Miami
Florida
Miami Cancer Institute
Miami
Florida
AdventHealth Orlando
Orlando
Florida
Nemours Children's Hospital
Orlando
Florida
Nemours Children's Clinic - Pensacola
Pensacola
Florida
Sacred Heart Hospital
Pensacola
Florida
Johns Hopkins All Children's Hospital
St. Petersburg
Florida
+ 188 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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