Reduced IV Fluids to Improve Clearance of HDMTX in Children w/Lymphoma or Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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To determine whether a reduced volume hydration regimen will lead to a shorter time to methotrexate clearance when compared to a standard intravenous (IV) hydration regimen.

Detailed Description
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This study uses a prospective randomized controlled crossover study design. Neither patients nor clinicians are blinded to the standard versus reduced intravenous fluids (IVF) regimen. Patients are randomized to begin with standard volume or reduced volume IVF. Over the course of 4 cycles of High Dose Methotrexate (HDMTX), patients alternate between standard and reduced volume post hydration fluids protocols.

Official Title
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Pilot Study on the Reduced Intravenous Fluids to Improve Clearance of High-Dose Methotrexate (HDMTX) in Children With Lymphoma or Acute Lymphoblastic Leukemia

Conditions
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Lymphoma, Acute Lymphoblastic Leukemia, Pediatric Cancer, Pediatric ALL, Pediatric Lymphoma

Intervention / Treatment
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* Drug: Intravenous fluids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of lymphoma or acute lymphoblastic leukemia Candidate for a minimum of 2 cycles HDMTX (5 g/m2) in the inpatient setting Creatinine clearance ≥ 65 mL/min by modified Schwartz equation Patients of childbearing potential must have a negative pregnancy test (serum or urine) Lactating female patients must agree not to nurse a child while on this trial All patients and/or their parents or legal guardians must provide written informed consent, with assent provided if applicable Exclusion Criteria: Trisomy 21 History of dialysis within 30 days prior to study registration or currently on dialysis Polyuric renal dysfunction Pregnancy Known or suspected pleural effusion Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study uses a prospective randomized controlled crossover study design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Hydration Regimen<br>In the standard intravenous fluid (IVF) protocol, following completion of HDMTX infusion, post HDMTX IVF will be initiated at 125 mL/m2/hr (no maximum mL/hr total rate). | Drug: Intravenous fluids<br>* Administration of post HDMTX intravenous fluids (IVF)<br>|
| Experimental: Reduced hydration regimen<br>The reduced intravenous fluid (IVF) protocol, post HDMTX IVF will be initiated at 62.5 mL/m2/hr following completion of HDMTX infusion. | Drug: Intravenous fluids<br>* Administration of post HDMTX intravenous fluids (IVF)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time elapsed (in hours) from end of HDMTX to a serum methotrexate level <0.1 micromol/L | To determine whether a reduced volume hydration regimen will lead to a shorter time to methotrexate clearance when compared to a standard IV hydration regimen by measuring serum methotrexate levels twenty-four hours following the end of the high dose methotrexate ( HDMTX) infusion, and continuing every twelve hours until the methotrexate level is less than 0.1 micromol/L. | 63 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of kidney toxicity | To determine the effect of a reduced volume hydration regimen on markers of kidney toxicity (nephrotoxicity) by evaluating serum creatinine levels from baseline levels as well as the maximum decrease in estimated glomerular filtration rate (GFR) utilizing the modified Schwartz equation, following each HDMTX cycle. | 84 Days | 
| Markers of fluid overload | To determine the effect of a reduced volume hydration regimen on markers of fluid overload by evaluating maximum weight gain during each hospitalization, and by evaluating the incidence of NCI Common Terminology Criteria for Adverse Events (CTCAE) version v5.0 ≥ grade 1 clinical sequelae of hydration such as facial edema, pulmonary edema, abdominal distension, extremity edema, and weight gain. | 84 Days | 
| Effects on therapy delays | To examine the effects of a reduced volume hydration regimen on treatment schedule by measuring the number of days subsequent therapy is delayed for reasons other than scheduling issues or preferences. | 84 Days | 
| Effects on development of severe mucositis | To examine the effects of a reduced volume hydration regimen on development of severe mucositis by measuring the incidence of grade ≥ 3 (CTCAE v5.0) mucositis. | 84 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Dose Methotrexate, HDMTX, Intravenous Fluids