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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Histologically confirmed Acute Lymphoblastic Leukemia or Acute Lymphoblastic Lymphoma (ALL) in patients in first remission at the start of Interim Maintenance I. HDMTX is administered during the phase of chemotherapy referred to as "Interim Maintenance I". Interim maintenance I occurs after induction and consolidation, is approximately 64 days in duration, and involves administration of four doses of HDMTX, with a dose given approximately every two weeks.

• Age 2-21 years with a weight of ≥ 13.2 lbs. and a hemoglobin ≥ 7.0

• Karnofsky/Lansky performance score of ≥ 50 (See Appendix II).

• Patients must receive high-dose Methotrexate (HDMTX; 5g/m2) as part of their standard or COG study chemotherapy. The current COG protocols which involve HDMTX include the following: AALL0232, AALL0434, and AALL1131.

• Patients must have a negative urine pregnancy test prior to enrollment and cannot be lactating.

• All subjects must have given signed, informed consent prior to registration on study.

Exclusion Criteria:

• Hypersensitivity to iohexol, iodine, other contrast material

• Hypersensitivity to shellfish

• Prior treatment with HDMTX