IRB Study Number 24-014
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objective
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).
1.2 Secondary Objectives
1.2.1 To examine the impact of levocarnitine prophylaxis on differences in the incidence of Grade ≥ 3 ALT or AST elevations during ALL Induction.
1.2.2 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.
Inclusion Criteria
3.2.1 Age
Age: ≥15 and <40 years at time of diagnosis
3.2.2 Diagnosis
Diagnosis: Newly Diagnosed B-ALL, T-ALL, Lymphoblastic Lymphoma (LLy), or Mixed-Phenotype Acute Leukemia/Lymphoma (MPAL)
Note: PH+ and PH-like acute leukemia are eligible (use of TKI or CRLF2-targeted concomitant medication must be documented, if used)
3.2.3 Organ Function Requirements
3.2.3.1 Adequate liver function defined as:
Conjugated bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin, and
SGPT (ALT) ≤ 225 U/L (≤5x ULN)*, and
SGOT (AST) ≤250 U/L (≤5x ULN)*
* 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.
3.2.3.2 Adequate renal function defined as:
A. For pediatric patients (age 15-17 years):
A 24-hour urine Creatinine clearance ≥ 30 mL/min/1.73 m2 OR
A GFR ≥ 30 mL/min/1.73 m2. GFR must be performed using one of the following methods:
- Estimated GFR (eGFR) ≥ 30 mL/min/1.73 m2
“Bedside” Schwartz formula (2009):
eGFR = 0.413 x (height/Scr)
An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped
- Measured GFR ≥ 30 mL/min/1.73 m2 (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).
B. For 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. Estimated creatinine clearance is based on actual body weight.
Estimated creatinine clearance = (140 - age) x weight in kg †
72 x creatinine* (mg/dl)
Multiply this number by 0.85 if the participant is a female.
† The kilogram weight is the participant weight with an upper limit of 140% of the ideal body weight (IBW).
* Actual lab serum or plasma creatinine value with a minimum of 0.7 mg/dL.
An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc
3.2.4 Treatment Plan
BFM, 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/ m2 (dose-capping permitted per primary regimen)
Note: Co-enrollment on a therapeutic consortia trial is not required.
Exclusion Criteria
3.2.5 Patients with the following conditions are not eligible
a) Down Syndrome
b) Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille Syndrome, primary sclerosing cholangitis, other)
c) Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig ≥Stage 3)
d) Unable to tolerate oral formulation of study drug at enrollment
3.2.6 Prior Therapy
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.
Please see Section 4.1 for the concomitant therapy restrictions for patients during treatment.
3.2.7 Pregnancy and Breastfeeding
3.2.7.1 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.
3.2.7.2 Lactating females who plan to breastfeed their infants.
3.2.7.3 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
