Levocarnitine for Chemotherapy-Related Liver Protection in Leukemia and Lymphoma

Recruiting at 242 trial locations

Overseen By Robert G. Irwin

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding levocarnitine to standard chemotherapy can better protect the liver in people with certain types of leukemia and lymphoma. Levocarnitine, a natural nutrient, may help reduce liver damage caused by asparaginase, a common chemotherapy drug that often affects the liver, especially in certain groups. People newly diagnosed with these cancers who have not had prior chemotherapy might be a good fit for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking ursodiol, you must stop it 7 days before meeting the laboratory criteria for the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that levocarnitine is generally safe for people. It is a natural substance produced by the body and found in many foods. Some studies have found that levocarnitine can help protect the liver, especially during chemotherapy. For instance, one study suggested that taking levocarnitine for 60 days improved liver enzyme levels, which indicate liver health.

In lab studies (not involving people), levocarnitine prevented liver damage from asparaginase, a common chemotherapy drug. This suggests it might reduce liver harm during treatment. Additionally, levocarnitine is already used to treat low carnitine levels in the body, which can otherwise lead to liver and other organ damage.

Overall, evidence suggests levocarnitine is well-tolerated and may help protect the liver during chemotherapy. However, it is always important to consult a healthcare provider before starting any new treatment or supplement. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Levocarnitine is unique because it serves a protective role for the liver during chemotherapy, addressing a key concern for patients with leukemia and lymphoma. Unlike traditional chemotherapy drugs like pegaspargase, which focus on targeting cancer cells, levocarnitine aims to prevent liver damage caused by these treatments. It acts by potentially reducing conjugated hyperbilirubinemia, a condition that can result from chemotherapy, thus offering a safeguard for the liver without altering the standard cancer-fighting regimen. Researchers are excited about levocarnitine because it could enhance the safety of chemotherapy, allowing patients to receive effective cancer treatment with reduced risk of liver complications.

What evidence suggests that levocarnitine could be an effective treatment for liver protection in leukemia and lymphoma patients?

Research suggests that levocarnitine, which participants in this trial may receive, might help protect the liver during chemotherapy for leukemia and lymphoma. Studies have shown that levocarnitine could reduce liver damage caused by asparaginase, a common drug in these cancer treatments. As a natural nutrient used by the body for energy, insufficient levels of levocarnitine are linked to liver problems. Early findings also indicate that levocarnitine does not interfere with chemotherapy's effectiveness. These insights offer hope that levocarnitine can lower the risk of serious liver damage during treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Etan Orgel

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05602194

NCT05602194 | Studying the Effect of Levocarnitine in ... This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver ...

2. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/ACCL1931-031125

Studying the Effect of Levocarnitine in Protecting the Liver ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7305023/

Levocarnitine does not impair chemotherapy cytotoxicity ... Together, our findings show that LC supplementation is a safe strategy to prevent/reverse ASNase-induced toxicities in preclinical models. Keywords: Acute ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03148

Levocarnitine to Reduce Hepatotoxicity in Patients with ... This early phase I trial tests the safety, side effects, and effectiveness of levocarnitine given during induction and consolidation therapy for patients ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20579689

Studying the Effect of Levocarnitine in Protecting the Liver ... The purpose of this study is to compare the effect of adding levocarnitine to standard chemotherapy vs. standard chemotherapy alone in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11782257/

Effects of oral Lcarnitine supplementation on liver enzymes in ... The results of this study suggested that a 60-day Lcarnitine treatment can improve liver enzyme levels and thus prevent the extent of liver damage during the ...

7. webmd.com webmd.com/vitamins-supplements/ingredientmono-1026-L-CARNITINE.aspx

L-Carnitine - Uses, Side Effects, and More Toxicity caused by valproic acid seems to be linked with L-carnitine deficiency. Taking L-carnitine by mouth or by IV can prevent liver toxicity from valproic ...