Clinical trial NCT05311254: A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia
Official title: A Multicenter Randomized Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia in Hematological Patients: Efficacy and Microbiological Safety
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Febrile Neutropenia
Lead sponsor: Fundación para la Investigación Biosanitaria del Principado de Asturias
Sponsor class: OTHER
Collaborators: name: Instituto de Investigación Marqués de Valdecilla
name: Instituto de Salud Carlos III
First posted: 2022-04-05
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, prospective, open-label
Primary purpose: PREVENTION

Brief summary: Randomized phase 3 trial to compare efficacy and safety of oral fosfomycin versus ciprofloxacin to prevent febrile neutropenia in patients with acute leukemia or recipients of hematopoietic stem cell transplant.

Detailed description: Multicenter, prospective, randomized, open label phase III trial to assess the efficacy and safety of oral fosfomycin vs. oral ciprofloxacin in the prevention of febrile neutropenia in patients with acute leukemia who are treated with intensive chemotherapy and/or are recipients of a hematopoietic stem cell transplant.

Non-inferiority design.

156 patients will be recruited: 78 in each arm

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

Primary outcomes:
measure: Febrile neutropenia of infectious origin
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary outcomes:
measure: Documented infections
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
measure: Use of broad spectrum antibiotics
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
measure: Overall survival
timeFrame: Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks.
measure: Drug related adverse events
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
measure: Evolution of resistome
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
measure: Microbiome evolution
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
measure: Microbiological safety
timeFrame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Instituto de Investigación Sanitaria del Principado de Asturias
state: Asturias
Study officials:
affiliation: Hospital Universitario Central Asturias
name: Teresa Bernal, MD PHD
role: PRINCIPAL_INVESTIGATOR
References: