A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy
Primary Aim
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 (AYAs, age 15-39 years).
Secondary Aims
To examine the impact of levocarnitine prophylaxis on differences in the incidence of Grade ≥ 3 ALT or AST elevations during ALL Induction.
To compare rates of minimal residual disease (MRD) positivity at end of Induction and describe MRD+ by end of Consolidation (EOC)
- Rutgers Cancer Institute of New Jersey
Inclusion Criteria
- >= 15 and < 40 years at time of diagnosis
- Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute
leukemia/lymphoma (MPAL)
- Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use
of tyrosine kinase inhibitors [TKI] or CRLF2- targeted concomitant medication
must be documented, if used)
- Conjugated bilirubin =< 1.5 x upper limit of normal (ULN) for age, regardless of
baseline bilirubin (within 7 days prior to enrollment), and
- Serum glutamate pyruvate transaminase (SGPT) (ALT) =< 225 U/L (=< 5x ULN) (within 7
days prior to enrollment), and
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50
U/L regardless of baseline
- SGOT (AST) =< 250 U/L (=< 5x ULN) (within 7 days prior to enrollment)
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline
- Berlin-Frankfurt-Munich (BFM), Children's Oncology Group (COG), or C10403-based
Induction regimen and must be inclusive of >= 1 dose of pegaspargase or calaspargase
pegol, and
- First dose of asparaginase must be planned within the first week of induction therapy,
and
- Dose of pegaspargase or calaspargase pegol must be >= 1,000 IU/ m^2 (dose-capping
permitted per primary regimen)
- Note: Co-enrollment on a therapeutic consortia trial is not required
- All patients and/or their parents or legal guardians must sign a written informed
consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria
- Down syndrome
- Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g.,
Alagille syndrome, primary sclerosing cholangitis, other)
- Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig >= stage 3)
- Patients who received chemotherapy or treatment for a prior malignancy are not
eligible
- The following are permitted: steroid prophase, hydroxyurea, or other
cytoreduction prior to initiation of Induction chemotherapy (must be documented)
and chemotherapy for current diagnosis (i.e. initiation of Induction therapy
within enrollment window). Chemotherapy prior to enrollment for treatment of a
non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also
permitted and must be documented
- Female patients who are pregnant since fetal toxicities and teratogenic effects in
humans are unknown for study drug. A pregnancy test is required for female patients of
childbearing potential
- Lactating females who plan to breastfeed their infants
- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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