Levocarnitine and Vitamin B Complex in Treating PEG-Asparaginase or Inotuzumab Ozogamicin-Induced Hyperbilirubinemia in Patients With Acute Lymphoblastic Leukemia

Mitochondrial Cofactors for the Treatment of Hyperbilirubinemia Due to PEG-Asparaginase and or Inotuzumab Ozogamicin in Patients With Acute Lymphoblastic Leukemia (ALL)

This phase II trial studies how well levocarnitine and vitamin B complex works in treating abnormal high liver enzyme levels (hyperbilirubinemia) caused by treatment with PEG-asparaginase or inotuzumab ozogamicin in patients with acute lymphoblastic leukemia. Amino acids, such as levocarnitine, may work in normalizing liver enzyme levels due to treatment. Vitamin B complex is a dietary supplement that may be used for patients with nutritional deficiencies. Giving levocarnitine and vitamin B complex may work better in treating hyperbilirubinemia in patients with acute lymphoblastic leukemia.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; Hyperbilirubinemia
• Intervention / Treatment: Dietary supplement: Levocarnitine; Drug: Vitamin B Complex

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of levocarnitine in combination with vitamin B complex in treating PEG-asparaginase (PEG) or inotuzumab ozogamicin (INO) induced hyperbilirubinemia (total bilirubin [Tbili] > 3 x upper limit of normal [ULN]) in patients (pts) with acute lymphoblastic leukemia (ALL).

SECONDARY OBJECTIVES:

I. To evaluate chemotherapy dose intensity in patients treated with PEG-asparaginase or inotuzumab ozogamicin.

II. To characterize the safety, tolerability, and adverse event profile of levocarnitine and vitamin B for the treatment of hyperbilirubinemia.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

Patients receive levocarnitine intravenously (IV) over 2-3 minutes every 6 hours up to 4 times a day (inpatient) or orally (PO) three times a day (TID) (outpatient). Patients also receive vitamin B complex PO twice daily (BID). Treatment continues for up to 30 days after the last dose of either PEG-asparaginase or inotuzumab, or until Tbili of ≤ 1.5 x ULN or at least a 50% reduction in peak Tbili is achieved.

After completion of study treatment, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elias Jabbour, MD; Phone Number: 713-792-4764; Email: ejabbour@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Principal Investigator: Elias Jabbour
      • Contact: Elias Jabbour; Phone Number: 713-792-4764

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients at least 18 years of age.
• Non-English speakers may be enrolled.
• Patients with a diagnosis of ALL who are receiving treatment with PEG-asparaginase or inotuzumab ozogamicin with Tbili > 3 x ULN
• Signed informed consent

Exclusion Criteria:

• Pregnant or nursing women
• Known hypersensitivity to levocarnitine or vitamin B complex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (levocarnitine, vitamin B complex); Patients receive levocarnitine IV over 2-3 minutes every 6 hours up to 4 times a day (inpatient) or PO TID (outpatient). Patients also receive vitamin B complex PO BID. Treatment continues for up to 30 days after the last dose of either PEG-asparaginase or inotuzumab, or until Tbili of ≤ 1.5 x ULN or at least a 50% reduction in peak Tbili is achieved.

Dietary supplement: Levocarnitine; Given IV; Other Names: L-carnitine; Carnitor; Drug: Vitamin B Complex; Given PO; Other Names: Becotin; Neurobion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates	Will be defined by normalization of hyperbilirubinemia. Response rates will be estimated along with the 95% confidence interval. The duration of time to hyperbilirubinemia normalization of at least 50% reduction in peak total bilirubin will be estimated using the Kaplan-Meier method.	Up to 30 days after completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of chemotherapy dose intensity	Descriptive statistics will be used to summarize secondary endpoints. The incidence rates of binary secondary endpoints will be estimated, along with the 95% confidence intervals.	Up to 30 days after completion of treatment
Incidence of adverse events	Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Descriptive statistics will be used to summarize secondary endpoints. The incidence rates of binary secondary endpoints will be estimated, along with the 95% confidence intervals. Safety data will be summarized by adverse event (AE) category, severity and frequency. The proportion of patients with AEs will be estimated.	Up to 30 days after completion of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to hyperbilirubinemia normalization	The time to hyperbilirubinemia normalization or achieving at least a 50% reduction in peak total bilirubin will be compared to historical controls using the Log rank test. Competing risk analysis will be considered in the case that patients died before bilirubin normalization or at least a 50% reduction in peak total bilirubin is achieved.	From the start of study treatment up to 30 days after completion of treatment

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2018
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2036

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hyperbilirubinemia; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex
• Other Study ID Numbers: 2017-0978 (Other Identifier: M D Anderson Cancer Center); NCI-2018-01253 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No