Prediction of Excretion and Toxicity of High Dose Methotrexate in Children and Adolescents With ALL
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02133599|
Recruitment Status : Active, not recruiting
First Posted : May 8, 2014
Last Update Posted : July 24, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|ALL||Drug: IOHEXOL||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prediction of Excretion and Toxicity of High Dose Methotrexate in Children and Adolescents With Acute Lymphoblastic Leukemia and Lymphoma|
|Actual Study Start Date :||July 24, 2014|
|Estimated Primary Completion Date :||September 30, 2019|
|Estimated Study Completion Date :||September 30, 2019|
All patients will receive two Iohexol clearance tests, 5 mL each time before cycle 1 and 4 of HDMTX
Patients receive 5 mL of Iohexol prior to cycle 1 and 4 of HDMTX
Other Name: Iohexol, Omnipaque 300
- Change in Iohexol clearance results [ Time Frame: An expected average of 6 weeks or more between the two Iohexol clearances ]A change from baseline Iohexol clearance results after about six weeks
- Change in serum creatinine [ Time Frame: An expected average of about 6 weeks between measures ]A change from baseline serum creatinine results after about six weeks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02133599
|United States, Illinois|
|Ann & Robert H. Lurie Children's Hosptial of Chicago|
|Chicago, Illinois, United States, 60611|
|Study Chair:||Amy Walz, MD||Ann & Robert H. Lurie Children's Hosptial of Chicago|