A multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients: efficacy and microbiologic safety.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Y La Innovacion Biosanitaria Del Principado De Asturias

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Not possible to specify

Decision date (initial)

2025-01-21

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520336-14-00

EudraCT number

2021-000354-25

ClinicalTrials.gov

NCT05311254

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To demonstrate non-inferiority in efficacy of oral fosfomycin versus oral ciprofloxacin in preventing febrile neutropenia in patients with acute leukemia treated with intensive chemotherapy and/or recipients of
hematopoietic stem cell transplantation hematopoietic stem cell transplantation.

Secondary objectives 6

1. Febrile neutropenia of infectious etiology
2. Compare overall survival from baseline to resolution of neutropenia in both treatment arms
3. To evaluate the safety and tolerability of both prophylactic strategies.
4. Perform surveillance cultures to determine the rate of Gram-negative multiresistant colonization (GNMRB), analyze the time course of colonization, and identify clinical factors associated with the clearance or persistence of GNMRB bacteria in the gut of previously colonized patients.
5. To evaluate the utility of a metagenomic approach in the identification of underdetected colonization, as compared to traditional surveillance cultures.
6. To analyze changes in the fecal microbiome of patients from initiation of chemotherapy to resolution of neutropenia and compare these changes between both treatment arms

Conditions and MedDRA coding

Post-chemotherapy neutropenia with high risk of developing infection in patients with acute leukemia undergoing induction, autologous or allogeneic hematopoietic stem cell transplantation (HSCT).

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subjects must be able to understand the study procedures, comply with them, and give written informed consent prior to any specific study procedure.
2. Adult subjects ≥ 18 years of age with a diagnosis of acute leukemia who are to receive their first course of chemotherapy or adult subjects ≥ 18 years of age who are candidates for a first stem cell transplant.
3. Expected neutropenia of 100x109/L lasting at least seven days. In the case of an expected range of 100-500x109/L neutropenia lasting seven days or longer, at least one of the following risk factors for infection must be present:
4. b. Expected grade 3-4 mucositis. c. Age ≥65 years. d. Comorbidity index (HCTI) ≥3. e. Serum albumin< 35 g/L. f. Total dose of etoposide > 500 mg/m2. g. Total dose of cytarabine > 1 g/m2. h. Active or refractory neoplasia at the time of stem cell transplantation.
5. Performance status (Eastern Cooperative Oncology Group, ECOG) of 0 to 3.
6. Adequate organ function defined as: Adequate organ function defined as: - Liver : bilirubin, alkaline phosphatase or SGOT < 3 times the upper limit of normal (unless attributable to tumor activity). - Renal : creatinine ≤ 250 μmol/l (2.5 mg/dL) (unless attributable to AML activity).
7. Life expectancy greater than 3 months
8. Women of childbearing age should not be pregnant or breastfeeding and should have a negative pregnancy test at the time of screening. Women of childbearing age and men with female partners of childbearing age must agree to practice 2 highly effective contraceptive measures and must agree not to become pregnant or father a child while receiving any study therapy and for at least 3 months after completion of treatment.

Exclusion criteria 5

1. Hypersensitivity to fluoroquinolones or fosfomycin.
2. Treatment with broad-spectrum antimicrobial therapy within 4 weeks of the first study treatment.
3. Prior intensive chemotherapy or stem cell transplantation. Treatment with hydroxyurea or corticosteroids used to control white blood cell count is allowed
4. Fever of infectious origin or documented infection within 4 weeks of first study treatment
5. Presence of any serious psychiatric illness or physical condition that, in the judgment of the physicians, contraindicates the patient's inclusion in the clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. febrile neutropenia requiring antibacterial treatment
2. Absolute Neutrophil Count (ANR) >0.5x109/L
3. If the subject fails to achieve more than 0.5x109/L neutrophils the study will end when more than 60 days have elapsed since the onset of neutropenia, or on the first day of the next chemotherapy cycle (whichever is earlier)
4. death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Y La Innovacion Biosanitaria Del Principado De Asturias

Sponsor organisation

Fundacion Para La Investigacion Y La Innovacion Biosanitaria Del Principado De Asturias

Address

Avenida De Roma Sn

City

Oviedo

Postcode

33011

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Y La Innovacion Biosanitaria Del Principado De Asturias

Contact name

TERESA BERNAL

Public contact point

Organisation

Fundacion Para La Investigacion Y La Innovacion Biosanitaria Del Principado De Asturias

Contact name

TERESA BERNAL

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications