Comparing fosfomycin and ciprofloxacin for preventing febrile neutropenia

A Multicenter Randomized Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia in Hematological Patients: Efficacy and Microbiological Safety

This study is testing if the antibiotic fosfomycin can prevent fever and low white blood cell counts as well as ciprofloxacin in patients with acute leukemia who are getting intensive chemotherapy or stem cell transplants.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 156 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fundación para la Investigación Biosanitaria del Principado de Asturias (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Oviedo, Asturias)
• Trial ID: NCT05311254 on ClinicalTrials.gov

What this trial studies

This phase 3 trial aims to compare the efficacy and safety of oral fosfomycin versus ciprofloxacin in preventing febrile neutropenia in patients with acute leukemia undergoing intensive chemotherapy or those receiving hematopoietic stem cell transplants. It is a multicenter, prospective, randomized, open-label study designed to recruit 156 patients, with 78 assigned to each treatment arm. The study employs a non-inferiority design to evaluate whether fosfomycin is as effective as ciprofloxacin in this high-risk population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with acute leukemia who are about to receive their first intensive chemotherapy cycle or are candidates for their first stem cell transplant.

Not a fit: Patients who do not have acute leukemia or are not undergoing intensive chemotherapy or stem cell transplant may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer and effective alternative for preventing febrile neutropenia in vulnerable patients.

How similar studies have performed: Previous studies have shown promising results with similar antibiotic approaches in preventing infections in neutropenic patients, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Subjects who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
2. Adult subjects ≥ 18 years of age with acute leukemia diagnosis who are going to receive their first intensive chemotherapy cycle or adult subjects ≥ 18 years of age who are candidates to receive a first stem cell transplant.
3. Expected neutropenia 100x109/L lasting at least seven days. In case of expected neutropenia range 100-500x109/L lasting seven days or more, at least one of the following risk factors for infection must be present:

   1. Performance status (Eastern Cooperative Oncology Group, ECOG) ≥2.
   2. Expected mucositis grade 3-4.
   3. Age ≥65 years.
   4. Comorbidity Index (HCTI) ≥3.
   5. Serum albumin\< 35 g/L.
   6. Total dose of etoposide \> 500 mg/m2
   7. Total dose of cytarabine \> 1 g/m2
   8. Active or refractory neoplasia at the moment of stem cell transplant.
4. Performance status (Eastern Cooperative Oncology Group, ECOG) of 0 to 3.
5. Adequate organ function defined as:

   Liver: bilirubin, alkaline phosphatase, or SGOT \< 3 times the upper normal limit (unless it is attributable to tumor activity).

   Renal : creatinine ≤ 250 μmol/l (2.5 mg/dL) (unless it is attributable to AML activity).
6. Life expectancy higher than 3 months.
7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving any study therapy and for at least 3 months after completing treatment.

Exclusion Criteria:

1. Hypersensitivity to fluoroquinolones or fosfomycin.
2. Treatment with broad spectrum antimicrobial therapy within 4 weeks of first study treatment.
3. Prior Intensive chemotherapy or stem cell transplant. Treatment with hydroxyurea or corticosteroids used to control white blood cell counts are permitted.
4. Fever of infectious origin or documented infection within 4 weeks of first study treatment.
5. Presence of any severe psychiatric disease or physical condition that, according to the physicians criteria, contraindicates the inclusion of the patient into the clinical trial.
6. Subjects that have participated previously in this study

Where this trial is running

Oviedo, Asturias

• Instituto de Investigación Sanitaria del Principado de Asturias — Oviedo, Asturias, Spain (Recruiting)

Study contacts

• Principal investigator: Teresa Bernal, MD PHD — Hospital Universitario Central Asturias
• Study coordinator: Teresa Bernal, MD PHD

Conditions Febrile Neutropenia