Xylitol Dental Wipes for the Reduction of Bloodstream Infection Risk in Children With Acute Myeloid Leukemia

A Randomized Double-Blinded Trial of Xylitol Dental Wipes for the Prophylaxis of Bloodstream Infections From Oral Organisms in Pediatric Patients With Acute Myeloid Leukemia

This phase III trial compares the effect of xylitol dental wipes to dental wipes without xylitol for the reduction of bloodstream infection in children with acute myeloid leukemia (AML). Xylitol is a naturally occurring sugar compound found in fruits and vegetables. Xylitol has been shown to limit the growth of bacteria in the mouth, and to reduce cavities, plaque on the teeth, and inflammation of the gums. Treatment for AML includes chemotherapy. Patients receiving chemotherapy for AML have a risk of developing bloodstream infections. Bloodstream infections can make patients very sick, can contribute to delays in treatment, and can even cause death. In AML patients, bacteria or fungus (yeast) can sometimes enter the bloodstream from the mouth. Using xylitol dental wipes may help to reduce bloodstream infections in children being treated for AML.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Other: Electronic Health Record Review; Procedure: Biospecimen Collection; Other: Best Practice; Other: Xylitol-containing Oral Wipe; Drug: Placebo Administration

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the incidence rate of bloodstream infections (BSI) (BSI per 1000 patient-days) from oral organisms over 2 cycles of chemotherapy in children with acute myeloid leukemia (AML) randomized to xylitol-containing oral wipes (xylitol dental wipes) versus control wipes.

SECONDARY OBJECTIVE:

I. To compare the rate of BSI (BSI per 1000 patient-days) from any organism in patients randomized to xylitol dental wipes versus control wipes.

EXPLORATORY OBJECTIVES:

I. To compare the frequency of severe infection (defined as any infection or infestation falling under Common Terminology Criteria for Adverse Events [CTCAE] sepsis grade 4 or 5) in patients randomized to xylitol dental wipes versus control wipes.

II. To compare the frequency of fever and neutropenia episodes in patients randomized to xylitol dental wipes versus control wipes.

III. To compare the frequency of severe mucositis, using the Children's International Mucositis Evaluation Scale (ChIMES), in patients randomized to xylitol dental wipes versus control wipes in addition to CTCAE grade 3 and above mucositis.

IV. To evaluate changes in oral microbial composition in pediatric patients treated with xylitol versus control wipes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard chemotherapy containing cytarabine intravenously (IV) on study and receive a xylitol dental wipe intraorally twice daily (BID) to the teeth and gums at the start of the chemotherapy cycle and continuing for up to 30 days or until absolute neutrophil count (ANC) >= 100/u/L following nadir. Treatment continues for 2 consecutive cycles of chemotherapy. Additionally, patients may optionally undergo saliva sample collections throughout the study.

ARM II: Patients receive standard chemotherapy containing cytarabine IV on study and receive a non-xylitol dental wipe intraorally BID to the teeth and gums at the start of the chemotherapy cycle and continuing for up to 30 days or until ANC >= 100/u/L following nadir. Treatment continues for 2 consecutive cycles of chemotherapy. Additionally, patients may optionally undergo saliva sample collections throughout the study.

After completion of study treatment, patients are followed over the next cycle of chemotherapy or if chemotherapy is complete, for 90 days after the start of the last cycle of chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 556
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94611
      • Recruiting
      • Kaiser Permanente-Oakland
      • Contact: Site Public Contact; Phone Number: 877-642-4691; Email: Kpoct@kp.org
      • Principal Investigator: Aarati V. Rao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must be ≥ 1 year to ≤ 25 years old at enrollment.
• Patient must have a diagnosis of AML according to the 2016 World Health Organization classification with or without extramedullary disease. Patients with either newly diagnosed or relapsed AML are eligible as long as they meet the planned treatment criteria.

• Patient should be planned to receive at least 2 consecutive cycles of myelosuppressive chemotherapy. Each cycle must:

  • Contain IV cytarabine (liposomal formulations allowed), and
  • The duration of severe neutropenia should be expected to be ≥ 7 days. Hematopoietic stem cell transplantation (HSCT) conditioning cannot count as one of the two required planned cycles.

Note: Patients do not need to be co-enrolled on an upfront AML treatment protocol study, but co-enrollment is permitted.

• Minimum of one visible or erupted tooth.
• Agree to avoid xylitol containing gum or toothpaste during intervention period.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria:

• Patients with Down syndrome-associated AML.
• Prior therapy: Prior radiation treatment for cancer of oral cavity, head or neck in past 6 months per study participant's medical record.
• Patients with known history of allergy to xylitol.
• Patients with known history of allergy to grapes or grape flavoring.
• Patients who are actively being treated for an oral organism related blood stream infection.
• Patients for whom the practitioner believes are unable to comply with use of oral dental wipes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (xylitol dental wipe); Patients receive standard chemotherapy containing cytarabine IV on study and receive a xylitol dental wipe intraorally BID to the teeth and gums at the start of the chemotherapy cycle and continuing for up to 30 days or until ANC >= 100/u/L following nadir. Treatment continues for 2 consecutive cycles of chemotherapy. Additionally, patients may optionally undergo saliva sample collections throughout the study.	Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Other: Electronic Health Record Review; Ancillary studies; Procedure: Biospecimen Collection; Undergo saliva sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Best Practice; Given standard chemotherapy; Other Names: standard of care; standard therapy; Other: Xylitol-containing Oral Wipe; Given intraorally; Other Names: Spiffies (TM) Xylitol Wipes; Xylitol Wipes
Active Comparator: Arm II (non-xylitol dental wipe); Patients receive standard chemotherapy containing cytarabine IV on study and receive a non-xylitol dental wipe intraorally BID to the teeth and gums at the start of the chemotherapy cycle and continuing for up to 30 days or until ANC >= 100/u/L following nadir. Treatment continues for 2 consecutive cycles of chemotherapy. Additionally, patients may optionally undergo saliva sample collections throughout the study.	Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Other: Electronic Health Record Review; Ancillary studies; Procedure: Biospecimen Collection; Undergo saliva sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Best Practice; Given standard chemotherapy; Other Names: standard of care; standard therapy; Drug: Placebo Administration; Given intraorally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bloodstream infections (BSI) from oral flora	Will report the estimated oral organism BSI incidence rates by arm as number of events per 1000 patient-days. Will also report the incidence rate ratio under a Poisson regression model contrasting incidence rates of oral organism BSI for the treatment relative to control arm and the corresponding 95% confidence interval.	Up to 37 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of BSI from any organism	Will report the estimated BSI incidence rates by arm as number of events per 1000 patient-days. Will also report the incidence rate ratio under a Poisson regression model contrasting incidence rates of BSI for the treatment relative to control arm and the corresponding 95% confidence interval.	Up to 37 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutropenic fever episodes	Will report the proportion of patients who experience one or more episodes of febrile neutropenia while on study by arm as well as corresponding 95% confidence intervals.	Up to 90 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study
Oral microbial layout (as measured by beta diversity using the Bray-Curtis dissimilarity index)	Will report the mean of Bray-Curtis dissimilarity index values by arm, using the final specimen (saliva) collection timepoint for each patient. Will report corresponding 95% confidence intervals.	Up to 42 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study
Severe infection (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or higher sepsis)	Will report the proportion of patients who experience one or more episodes of febrile neutropenia while on study by arm as well as corresponding 95% confidence intervals.	Up to 90 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study
Severe mucositis (CTCAE grade 3 or higher)	Will report the proportion of patients who experience one or more episode of severe mucositis while on study by arm as well as corresponding 95% confidence intervals.	Up to 90 days after the start date of the second cycle of chemotherapy that occurs while the patient is enrolled on study

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Investigators: Principal Investigator: Jennifer J Wilkes, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2026
• Primary Completion (Estimated): January 15, 2032
• Study Completion (Estimated): January 15, 2033

Study Registration Dates

• First Submitted: May 29, 2025
• First Submitted That Met QC Criteria: June 6, 2025
• First Posted (Actual): June 15, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Health Services Administration; Health Care Quality, Access, and Evaluation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Nucleic Acids, Nucleotides, and Nucleosides; Quality of Health Care; Quality Indicators, Health Care; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Arabinonucleosides; Guidelines as Topic; Quality Assurance, Health Care; Cytarabine; Standard of Care; Specimen Handling; Practice Guidelines as Topic
• Other Study ID Numbers: ACCL2531 (Other Identifier: CTEP); UG1CA189955 (U.S. NIH Grant/Contract); U24CA196173 (U.S. NIH Grant/Contract); NCI-2025-03832 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); COG-ACCL2531 (Other Identifier: DCP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes