CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia)

Study Overview
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Brief Summary
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CiproPAL is a randomised trial comparing daily ciprofloxacin with local standard care during the induction phase of paediatric ALL treatment, and aims: To assess the efficacy of ciprofloxacin prophylaxis in the reduction of infection during the induction phase of treatment for paediatric Acute Lymphoblastic Leukaemia within the ALLTogether-1 Trial. To evaluate the impact of ciprofloxacin prophylaxis on antimicrobial resistance, both of invasive infections and colonising organisms.

Detailed Description
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This is a multi-centre randomised trial of prophylactic ciprofloxacin (10mg/kg BD, enteral/IV) versus standard of care during the neutropenic period of induction (with an internal pilot study) in patients aged 1-17 years with de-novo ALL treated on ALLTogether-1. Exclusion criteria include: patients with Down syndrome (who already receive ciprofloxacin prophylaxis), contraindication to fluoroquinolones, non-consent to ALLTogether-1 or CiproPAL. AMR of colonising organisms will be assessed with stool or peri-rectal swab cultures performed at five timepoints within the first year. Longer term invasive infection AMR monitoring will include sensitivity testing of all organisms isolated in confirmed infection for the duration of ALLTogether-1. The primary outcome is the rate of sterile site bacterial infections during induction, evaluated by intention to treat analysis. Secondary outcomes include rates of febrile episodes, febrile neutropenia, severe infection and infection-related death; rates of AMR; antibiotic exposure; secondary infections; and quinolone side effects. A model-based health economic analysis will be undertaken. Using a conservative effect estimate of 40% reduction in bacteraemia (i.e. a reduction from 15% to 9%) 1052 patients randomised 1:1 gives 85% power with a 5% 2-sided alpha.

Official Title
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CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia): A Randomised Trial to Assess the Use of Ciprofloxacin Prophylaxis to Prevent Bacterial Infection in Children Treated on the Induction Phase of the ALLTogether-1 Treatment Protocol

Conditions
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Acute Lymphoblastic Leukaemia - Category

Intervention / Treatment
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* Drug: Ciprofloxacin
* Drug: Antibiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paediatric patients (1-17 years inclusive) with de-novo Acute Lymphoblastic Leukaemia treated on ALLTogether-1 in the UK in the first 5 days of therapy. Written informed consent Exclusion Criteria: Non-participants of the ALLTogether-1 trial Patients with Down syndrome who already receive ciprofloxacin prophylaxis Chronic active arthritis Other contraindication to fluoroquinolones

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised trial of prophylactic ciprofloxacin (10mg/kg BD, enteral/IV) versus standard of care during the neutropenic period of induction (with an internal pilot study) in patients aged 1-17 years with de-novo ALL treated on ALLTogether-1. Exclusion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cirprofloxacin prophylaxis<br>prophylactic ciprofloxacin (10mg/kg BD, enteral/IV) | Drug: Ciprofloxacin<br>* prophylactic ciprofloxacin (10mg/kg BD, enteral/IV)<br>|
| Active Comparator: Standard of care<br>standard of care | Drug: Antibiotic<br>* Standard of care antibiotic as per local policy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of sterile site bacterial infections during induction | rate of sterile site bacterial infections during induction | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rates of febrile episodes | rates of febrile episodes | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 
| rates of febrile neutropenia | rates of febrile neutropenia | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 
| rates of severe infection and infection-related death | severe infection rates and deaths from infection | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 
| rates of AMR (antimicrobial resistance) | rates of AMR | Until the end of trial approx 10 years (from randomisation until the end of trial declaration in 2031) | 
| rates of antibiotic exposure | rates of antibiotic exposure | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 
| rates of secondary infections | rates of secondary infections | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 
| quinolone side effects | quinolone side effects | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic prophylaxis