CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia)

Not Applicable

Recruiting

• Conditions: Acute Lymphoblastic Leukaemia - Category
• Interventions: Drug: Ciprofloxacin; Drug: Antibiotic

• Registration Number: NCT04678869
• Lead Sponsor: University College, London

Brief Summary

CiproPAL is a randomised trial comparing daily ciprofloxacin with local standard care during the induction phase of paediatric ALL treatment, and aims:

1. 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.

2. To evaluate the impact of ciprofloxacin prophylaxis on antimicrobial resistance, both of invasive infections and colonising organisms.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-12-05
• Study First Submitted QC: 2020-12-16
• Study First Posted: 2020-12-22
• Study Start: 2022-06-29
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-08
• Primary Completion: 2025-12-01
• Study Completion: 2031-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1052

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, up to 14 days is acceptable.
• Written informed consent

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cirprofloxacin prophylaxis	Ciprofloxacin	prophylactic ciprofloxacin (10mg/kg BD, enteral/IV)
Standard of care	Antibiotic	standard of care

Primary Outcome Measures

Name	Time	Method
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)	rate of sterile site bacterial infections during induction

Secondary Outcome Measures

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

Trial Locations

Locations (14)

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

Nottingham Children's Hospital; 🇬🇧 Nottingham, United Kingdom

Bristol Royal Hospital for Children; 🇬🇧 Bristol, United Kingdom

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom

Royal Victoria Infirmary; 🇬🇧 Newcastle, United Kingdom

Leeds General Infirmary; 🇬🇧 Leeds, United Kingdom

Univeristy College Hospital London; 🇬🇧 London, United Kingdom

John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom

Royal Aberdeen Children's Hospital; 🇬🇧 Aberdeen, United Kingdom

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Alder Hey Children's Hospital; 🇬🇧 Liverpool, United Kingdom

Sheffield Children's Hospital; 🇬🇧 Sheffield, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom