Prediction of Excretion and Toxicity of High Dose Methotrexate in Children and Adolescents With ALL
Status:
Completed
Trial end date:
2019-02-27
Target enrollment:
Participant gender:
Summary
Each year approximately 2,900 children and adolescents less than 20 years old are diagnosed
with acute lymphoblastic leukemia or acute lymphoblastic lymphoma in the United States. (For
the purposes of this protocol, ALL will be used to refer to patients with either acute
lymphoblastic leukemia or acute lymphoblastic lymphoma as patients are treated in the same
manner.) High-dose methotrexate (HDMTX; 5 g/m2) remains an important component of standard
treatment for most ALL patients. However, high plasma and intracellular MTX concentrations
(defined as a MTX level of >1 µmol/L at 42 hours and > 0.40 µmol/L at 48 hours) can quickly
lead to acute kidney, bone marrow, liver, skin, central nervous system, and gastrointestinal
toxicities requiring extended hospitalization and delays in subsequent chemotherapy
treatments.
This study seeks to identify more sensitive markers of kidney injury that could serve as
better predictors of delayed excretion and/or toxicity of HDMTX. This study is a pilot
repeated-measures feasibility study.
Hypothesis 1: Directly measured GFR (mGFR, a type of test to measure the filtering rate of
kidneys) by iohexol clearance obtained prior to HDMTX will demonstrate greater sensitivity
and specificity for prediction of delayed MTX excretion and/or toxicity in children and
adolescents with ALL than serum creatinine (sCr) alone or sCr used for eGFR calculation. If
this study proves that mGFR is a better predictor of delayed MTX excretion and/or toxicity,
then another study will be developed in the future to determine if modifying the HDMTX dose
or adjusting supportive care based on mGFR will prevent delayed clearance and toxicity
without impacting patient survival.
Hypothesis 2: Those participants prospectively demonstrating delayed MTX excretion or
toxicity will exhibit elevation of kidney injury biomarkers less than 24 hours following
initiation of HDMTX infusion compared to pre-chemotherapy measurements. These biomarkers will
increase prior to a measurable sCr elevation.
Phase:
N/A
Details
Lead Sponsor:
Ann & Robert H Lurie Children's Hospital of Chicago