A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy

R
Rachael Schulte

Primary Investigator

Administratively Closed
15 years - 40 years
All
Phase N/A
1 participants needed
2 Locations

Brief description of study

What is this study about?
  1. 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)
  2. To examine the impact of levocarnitine prophylaxis on differences in the incidence of Grade more than or equal to 3 ALT or AST elevations during ALL Induction.
  3. To compare rates of minimal residual disease (MRD) positivity at end of Induction and describe MRD+ by end of Consolidation (EOC) in those receiving ALL Induction chemotherapy with and without levocarnitine.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 

 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What happens during study participation?

Experimental: Arm A (levocarnitine, standard of care chemotherapy)
Patientsve levocarnitine PO or IV prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.

Active Comparator: Arm B (standard of care chemotherapy)
Patientsve standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.

Experimental: Arm C (rescue levocarnitine)
PatientsArms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO or IV supplementation until resolution of conjugated hyperbilirubinemia =< 3g/dL (or start of consolidation or the next treatment phase, whicheverurs first).

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2), BCR-ABL1, B Acute Lymphoblastic Leukemia, BCR-ABL1-Like Lymphoblastic Lymphoma Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia
  • Age: 15 years - 40 years
  • Gender: All

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

Updated on 26 Nov 2024. Study ID: PHO-COG-ACCL1931, 20687

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