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

Phase 1

Completed

• Conditions: Acute Lymphoblastic Leukemia; Pediatric ALL; Lymphoma; Pediatric Cancer; Pediatric Lymphoma
• Interventions: Drug: Intravenous fluids

• Registration Number: NCT03964259
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-05-23
• Study First Submitted QC: 2019-05-23
• Study First Posted: 2019-05-28
• Study Start: 2019-10-02
• Primary Completion: 2022-12-07
• Study Completion: 2022-12-28
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-08
• Last Update Posted: 2024-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Standard Hydration Regimen	Intravenous fluids	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).
Reduced hydration regimen	Intravenous fluids	The reduced intravenous fluid (IVF) protocol, post HDMTX IVF will be initiated at 62.5 mL/m2/hr following completion of HDMTX infusion.

Primary Outcome Measures

Name	Time	Method
Time elapsed (in hours) from end of HDMTX to a serum methotrexate level <0.1 micromol/L	63 Days	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.

Secondary Outcome Measures

Name	Time	Method
Markers of kidney toxicity	84 Days	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.
Effects on therapy delays	84 Days	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.
Markers of fluid overload	84 Days	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.
Effects on development of severe mucositis	84 Days	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.

Trial Locations

Locations (1)

Virginia Commonwealth University/ Massey Cancer Center/ Children's Hospital of Richmond; 🇺🇸 Richmond, Virginia, United States