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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Acute Lymphoblastic Leukemia, Hyperbilirubinemia

Intervention / Treatment
-----------------
* Dietary Supplement: Levocarnitine
* Drug: Vitamin B Complex


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (levocarnitine, vitamin B complex)<br>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<br>* Given IV<br>* Other names: L-carnitine;Drug: Vitamin B Complex<br>* Given PO<br>* Other names: 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 |