Ignite Creation Date:
2025-12-25 @ 1:46 AM
Ignite Modification Date:
2026-01-06 @ 5:09 PM
Study NCT ID:
NCT05602194
Status:
RECRUITING
Last Update Posted:
2025-12-22
First Post:
2022-10-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
Sponsor:
Children's Oncology Group
Organization:
Study Overview
Official Title:
A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy
Status:
RECRUITING
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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) 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).
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).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-08058 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| ACCL1931 | OTHER | Children's Oncology Group | View | |
| COG-ACCL1931 | OTHER | DCP | View | |
| ACCL1931 | OTHER | CTEP | View | |
| U24CA196173 | NIH | None | https://reporter.nih.gov/quic… | View |
| UG1CA189955 | NIH | None | https://reporter.nih.gov/quic… | View |