Levocarnitine for Chemotherapy-Related Liver Protection in Leukemia and Lymphoma

Recruiting at 214 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must be taking: Asparaginase

Disqualifiers: Down syndrome, Severe liver fibrosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

440 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Etan Orgel

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for young adults aged 15-39 with newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma, or MPAL. They must have liver function within certain limits and plan to receive asparaginase chemotherapy. Excluded are those with Down syndrome, inherited/autoimmune liver diseases, severe liver fibrosis, prior malignancy treatments (except specific allowed cases), pregnant or breastfeeding women, and those not using effective contraception.

Inclusion Criteria

Co-enrollment on a therapeutic consortia trial is not required

My bilirubin levels are within the normal range for my age.

I have received at least one dose of pegaspargase or calaspargase pegol as part of my cancer treatment.

Exclusion Criteria

My liver has severe scarring confirmed by tests.

I have had chemotherapy or treatment for another cancer before.

I am currently pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive induction chemotherapy with or without levocarnitine to assess its effect on liver toxicity

5 weeks

Weekly visits (in-person)

Rescue

Patients who develop conjugated hyperbilirubinemia may receive levocarnitine rescue treatment

Until resolution of hyperbilirubinemia or start of next phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Periodic visits (in-person and virtual)

Treatment Details

Interventions

• Levocarnitine

Trial Overview The study tests if Levocarnitine added to standard chemotherapy can protect the liver from damage caused by asparaginase in leukemia/lymphoma patients. It compares outcomes of patients receiving Levocarnitine plus chemotherapy against those receiving only standard chemo.

Participant Groups

Group I: Arm C (rescue levocarnitine) Experimental Treatment 1 Intervention

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 II: Arm A (levocarnitine, standard of care chemotherapy) Experimental Treatment 5 Interventions

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 III: Arm B (standard of care chemotherapy) Active Control 4 Interventions

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.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+