Reduced IV Fluids for Childhood Cancer

Overseen By Lindsey B Gwaltney, RN

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Virginia Commonwealth University

Disqualifiers: Trisomy 21, Dialysis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using less intravenous (IV) fluid helps children eliminate methotrexate, a chemotherapy drug, from their bodies more quickly. It compares two approaches: a standard fluid amount and a reduced fluid amount administered after methotrexate treatment. Children with lymphoma or acute lymphoblastic leukemia undergoing methotrexate treatment might be suitable candidates. The trial seeks a gentler method to manage fluid levels during chemotherapy. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that intravenous fluids are generally safe, but some risks exist. Studies have found that excessive fluid can lead to volume overload, where the body receives more fluid than it can handle. This can cause issues like difficulty breathing or kidney problems. Using less fluid might help avoid these complications.

Some studies suggest that isotonic fluids, which match the body's salt levels, can prevent issues like hyponatremia. Hyponatremia occurs when there isn’t enough sodium in the blood, leading to symptoms like headaches, confusion, or more serious problems if it worsens.

Overall, research supports the safety of using less intravenous fluid. While potential risks exist, careful monitoring can often manage them. Participants should discuss any concerns with the medical team conducting the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the fluid protocol being tested because it could make high-dose methotrexate (HDMTX) treatment safer and more efficient for kids with lymphoma or acute lymphoblastic leukemia. Unlike standard care, which uses a high volume of intravenous fluids to help clear the drug from the body, this trial is exploring a reduced hydration regimen. The hope is that by using less fluid, kids might experience fewer side effects, like swelling, while still effectively clearing the drug. If successful, this approach could lead to a more comfortable and manageable treatment experience for young patients.

What evidence suggests that this trial's hydration regimens could be effective for methotrexate clearance?

This trial will compare two hydration regimens following high-dose methotrexate (HDMTX) infusion. Research has shown that using less fluid after HDMTX might clear the drug from the body as effectively as the usual method. Participants in one arm of this trial will receive the standard hydration regimen, while those in another arm will receive a reduced hydration regimen. One study found that reducing the amount of fluid given through an IV after methotrexate treatment did not alter the drug's elimination rate, suggesting it could be as effective as the standard approach. This method was also found to be safe, which is important for patients. The goal is to achieve the same drug clearance while possibly reducing side effects related to excess fluid. More research is needed to confirm these findings, but the initial results are promising. ^{6 7 8 9 10}

Who Is on the Research Team?

Cady P Noda, PharmD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

Inclusion Criteria

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

Exclusion Criteria

Known or suspected pleural effusion

Trisomy 21

History of dialysis within 30 days prior to study registration or currently on dialysis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 4 cycles of High Dose Methotrexate (HDMTX) with alternating standard and reduced volume hydration regimens

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including effects on therapy delays, fluid overload, severe mucositis, and kidney toxicity

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intravenous fluids

How Is the Trial Designed?

Group I: Reduced hydration regimen Experimental Treatment 1 Intervention

The reduced intravenous fluid (IVF) protocol, post HDMTX IVF will be initiated at 62.5 mL/m2/hr following completion of HDMTX infusion.

Group II: Standard Hydration Regimen Active Control 1 Intervention

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).

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Published Research Related to This Trial

In a study of 2825 patients across 61 ICUs in Australia and New Zealand, the use of crystalloid fluids for resuscitation significantly increased from 28.9% in 2007 to 50.5% in 2013, indicating a shift towards these fluids in critical care.

The use of colloid fluids decreased notably during the same period, particularly gelatin-based colloids, which dropped from 28.9% to just 2.1%, suggesting a change in preference towards buffered salt solutions for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013. Hammond, NE., Taylor, C., Saxena, M., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03964259

Reduced IV Fluids to Improve Clearance of HDMTX in ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39868759/

Standard Versus Reduced Hydration to Improve Elimination of ... Conclusion: Reduced posthydration appeared to be safe and provided similar time to HDMTX elimination. A multicenter study is indicated to confirm the use of ...

3. ascopubs.org ascopubs.org/doi/10.1200/GO-24-00450

Intrainfusion Drug Monitoring and Algorithm-Based Dose ... For all infusions, we were able to achieve a mean hour 24 methotrexate level close to the projected 65 ± 15 μM. There were no statistically ...

4. withpower.com withpower.com/trial/phase-1-precursor-cell-lymphoblastic-leukemia-lymphoma-9-2019-436a9

Reduced IV Fluids to Improve Clearance of HDMTX in ... This trial is testing if giving patients less fluid through an IV after a high dose of methotrexate can help clear the drug faster compared to the usual amount ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6347087/

Feasibility of Outpatient High-Dose Methotrexate Infusions ... This feasibility study indicated that home administration of HD MTX is safe and cost effective in pediatric subjects with B-lineage ALL and is more tolerable.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10561811/

Closing the Fluid Gap: Improving Isotonic Maintenance ... More recent data have shown an increased risk of hyponatremia when using hypotonic IVF as maintenance, and death and encephalopathy have been reported. In ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9635800/

Intravenous Fluid Administration and the Risk of Adverse ... Volume overload, new oxygen requirement, acute chest syndrome, and acute kidney injury are potential adverse outcomes of inappropriate IVF use in VOC. There is ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735675722001590

Outcomes of CMS-mandated fluid administration among ... This systematic review and meta-analysis demonstrates that, while a 30 ml/kg fluid resuscitation does not appear to cause significant adverse events in septic ...

9. publications.aap.org publications.aap.org/pediatrics/article/142/6/e20183083/37529/Clinical-Practice-Guideline-Maintenance

Maintenance Intravenous Fluids in Children | Pediatrics Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVF could prevent the development of hyponatremia.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1553838919304324

Intravenous Fluid Therapy Is Associated with a Reduced ... We found that intravenous fluid therapy was associated with a decreased incidence of contrast-induced nephropathy.