Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
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.
Not Available
Phase III
Both
Not Available
Not Available
Not Available
National
Vanderbilt University
12-06-2023
Eligibility
15 Years to 40 Years
ALL
false
Inclusion Criteria:
>= 15 and 40 years at time of diagnosis
>= 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)
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
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
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
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
For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
PEDIATRIC PATIENTS (AGE 15-17 years): * A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR * A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment): * 1. Estimated GFR (eGFR) >= 30 mL/min/1.73 m\^2. * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped * 2. Measured GFR >= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
PEDIATRIC PATIENTS (AGE 15-17 years): * A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR * A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment): * 1. Estimated GFR (eGFR) >= 30 mL/min/1.73 m\^2. * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped * 2. Measured GFR >= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorcoc
ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorcoc
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
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
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
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 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
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Down syndrome
Down syndrome
Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other)
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)
Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig >= stage 3)
Unable to tolerate oral formulation of study drug at enrollment
Unable to tolerate oral formulation of study drug at enrollment
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
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
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
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
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
>= 15 and 40 years at time of diagnosis
>= 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)
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
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
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
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
For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
PEDIATRIC PATIENTS (AGE 15-17 years): * A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR * A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment): * 1. Estimated GFR (eGFR) >= 30 mL/min/1.73 m\^2. * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped * 2. Measured GFR >= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
PEDIATRIC PATIENTS (AGE 15-17 years): * A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR * A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment): * 1. Estimated GFR (eGFR) >= 30 mL/min/1.73 m\^2. * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped * 2. Measured GFR >= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorcoc
ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight * An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorcoc
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
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
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
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 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
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Down syndrome
Down syndrome
Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other)
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)
Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig >= stage 3)
Unable to tolerate oral formulation of study drug at enrollment
Unable to tolerate oral formulation of study drug at enrollment
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
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
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
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
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
