Febrile Neutropenia
Conditions
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
Interventions
DRUGFosfomycin Calcium
Oral fosfomycin, three times daily, starting from the first day of induction chemotherapy or conditioning until absolute neutrophil count \>0,5x109/L.
Sponsors
Instituto de Investigación Marqués de Valdecilla
Instituto de Salud Carlos III
Fundación para la Investigación Biosanitaria del Principado de Asturias
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Multicenter, randomized, prospective, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Febrile neutropenia of infectious origin | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Febrile neutropenia that requires antibacterial treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of broad spectrum antibiotics | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Index of days of antibiotics per hospitalization days. Antibiotics will be classified according the Watch/Reserve classification |
| Overall survival | Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks. | — |
| Drug related adverse events | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Incidence of Adverse Events (AE), severity and type of AEs. |
| Documented infections | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Rate and type of documented infections |
| Microbiome evolution | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Changes in the gut microbiome produced under both prophylactic strategies during the study period. |
| Microbiological safety | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Rate of patients colonized by multidrug resistant bacteria as determined by surveillance cultures |
| Evolution of resistome | Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum | Rate of patients colonized by multidrug resistant bacteria as determined by metagenomic sequencing |
Countries
Spain
Contacts
Primary ContactTeresa Bernal, MD PHD
Backup ContactJavier Fernandez Dominguez, BD
Outcome results
None listed