CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia) (CiproPAL)

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

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.

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.

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

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

Until the end of trial approx 10 years (from randomisation until the end of trial declaration in 2031)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)

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

Requests for de-identified data should be made in writing to the relevant trials group lead at the CR UK and UCL Cancer Trials Centre (https://www.ctc.ucl.ac.uk/DataSampleSharing.aspx)