A clinical study testing if a daily low dose of an antibiotic, ciprofloxacin, given during the first part of chemotherapy treatment to children with newly diagnosed ALL would reduce the risk of infection
| ISRCTN | ISRCTN21195635 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21195635 |
| EudraCT/CTIS number | 2021-000341-40 |
| IRAS number | 293372 |
| ClinicalTrials.gov number | NCT04678869 |
| Secondary identifying numbers | 129038, NIHR130848,1004004 |
- Submission date
- 08/01/2021
- Registration date
- 20/01/2021
- Last edited
- 12/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims:
Acute Lymphoblastic Leukaemia (ALL) is one of the commonest forms of childhood cancer. Treatment has improved and survival rates are now high. ALL treatment involves chemotherapy which reduces the child’s ability to fight infections. Infection is now one of the commonest causes of death in children with ALL, and this is most likely to happen in the first five weeks of treatment – called “Induction”.
In children with other types of leukaemia and in children whose ALL has come back after treatment (relapsed), it has been shown that giving a daily, low dose of antibiotics every day can reduce the risk of infection by about a half, but nobody has tested it in children the first time they have treatment for ALL.
A new research study to look at how best to treat childhood ALL called ALLTogether-1 is open in the UK and across Europe. Our study, called CiproPAL, will work alongside the ALLTogether-1 study in the UK. CiproPAL will aim to answer the question “Does adding a daily, low-dose antibiotic (called ciprofloxacin) during the first part of chemotherapy treatment (induction) reduce the risk of infection in children, age 1-17 years old, with new ALL?”
Who can participate?
Children, aged 1-17 years with new ALL and are taking part in the ALLTogether-1 research study. They will have give their consent to take part in CiproPAL or their parents give consents on their behalf.
What does the study involve?
Each child will receive either the antibiotic or no antibiotic – the decision will be made randomly by a computer. We will then look at whether they get infections.
We will do tests to see if the infections that make children unwell and whether the bacteria that usually live in us are more resistant to antibiotics. This will help to decide whether using ciprofloxacin is a good idea. The tests to see if the infections that make children unwell are resistant to antibiotics will be done as part of the normal care of the children – we will just collect the information to be used. The test for bacteria that live in us will be done by taking a sample of stool, or if the patient is finding it difficult to poo, a swab (a bit like cotton wool on a stick) that is rubbed onto the bottom. It does not hurt. The swab can be done by the
patient, their carer, or a healthcare professional. It can be done when they are awake or when they are having an anaesthetic (for their other leukaemia treatment). We will ask for 5 of these samples to be done for each child over a year from when they join CiproPAL. These samples (of stool or swabs) will be optional – patients can still take part in CiproPAL whether they are done or not.
What are the possible benefits and risks of participating?
Giving children regular antibiotics might change how well the infections respond to antibiotics in the future (“resistance”). Tests will be done to look at whether this happens on CiproPAL. We hope that children who receive the antibiotics will have less infections during the induction stage of their treatment.
Where is the study run from?
CiproPAL is being run in NHS children's hospitals in the UK, who are also seeing patients for the ALLTogether-1 research study.
When is the study starting and how long is it expected to run for?
December 2020 to December 2031
Who is funding the study?
National Institute of Health Research (NIHR) (UK)
Who is the main contact?
Stephanie Argue (public), ctc.cipropal@ucl.ac.uk
Dr Robert Phillips (scientific), bob.phillips@york.ac.uk
Contact information
Public
Haematology Trials Group
Cancer Research UK and UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
| Phone | +44 (0)207 679 9867 |
|---|---|
| ctc.cipropal@ucl.ac.uk |
Scientific
Centre for Reviews and Dissemination
University of York
York
YO10 5DD
United Kingdom
 ORCID ID |
0000-0002-4938-9673 |
|---|---|
| Phone | +44 (0)1904 321099 |
| bob.phillips@york.ac.uk |
Study information
| Study design | Interventional randomized controlled trial with internal pilot study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | 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 |
| Study acronym | CiproPAL |
| Study objectives | 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 |
| Ethics approval(s) |
1. Approved 20/08/2020, HCRW Wales (2 Redman Place, Cardiff, CF14 7EF, United Kingdom; +44 (0)292 2940931; HCRW.approvals@wales.nhs.uk), ref: 20/WM/0205 2. Approved 25/11/2021, London – Brent REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)2071048131; brent.rec@hra.nhs.uk), ref: 21/LO/0752 |
| Health condition(s) or problem(s) studied | Reduction in risk of infection during the induction phase of treatment for paediatric acute lymphoblastic leukaemia |
| Intervention | Treatment arm: Drug - Ciprofloxacin Intervention - Prophylactic ciprofloxacin (10mg/kg BD, enteral/IV), to be given daily during the induction phase (over 4 weeks) Control arm: Drug: Antibiotic Control - Standard of care antibiotic as per local policy Following pre-randomisation assessments, using an electronic randomisation system, eligible patients will be allocated to an intervention arm stratified by intensity of chemotherapy (low-intensity vs high-intensity), age (<10 years vs >10 years), antibiotic use at randomisation (patients given antibiotics at diagnosis for proven/suspected infection vs no antibiotics) and trial centre. Both arms will be followed up for at least 72 months in total (12 months of active follow-up and at least 60 months of passive follow-up) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Ciprofloxacin |
| Primary outcome measure | Rate of sterile site bacterial infections during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction, using patient records |
| Secondary outcome measures | Current secondary outcome measures as of 10/01/2025 were assessed using patient records unless otherwise noted: 1. Febrile episodes, febrile neutropenia, severe infection (defined as the need for organ support or critical care intervention) and infection-related death. 1.1. Fever is defined as temperature ≥38°C (as per CTCAE v5.0). 1.2. Febrile neutropenia is defined as neutrophil count ≤0.5x109/L and either a single temperature of >38.3°C or a sustained temperature of >38°C for more than one hour. 2. Antibiotic exposure relating to infections which result in an inpatient hospital stay: This will be reported as days on therapy per 100 patient days per antibiotic. Total exposure for IV antibiotics and IV+oral will be described. Separate analysis will be performed looking specifically at the differences: 2.1. Prophylactic antibiotics include ciprofloxacin (intervention), prophylaxis for Pneumocystis jirovecii infection (usually with co-trimoxazole on two days per week), and prophylaxis against urinary or respiratory infections. 2.2. Empirical antibiotics are those given prior to the identification of a specific infection and are usually defined within a centre’s febrile neutropenia protocol. 2.1. Treatment antibiotics are those targeted at a particular clinically or microbiologically defined infection. 3. Patterns of antimicrobial resistance and their changes over time in A) bacterial isolates from blood cultures or other sterile sites, B) stool or peri-rectal swab isolates. 3.1. Local sites to analyse, looking at standard resistance patterns and report for each antibiotic class as resistant, intermediate or sensitive. 4. Secondary infections: Clostridium difficile infections (see current definitions) and invasive fungal infections (following the 2020 EORTC definition). 5. Specific quinolone adverse effects, including tendinitis and tendinopathy, visual disturbance, seizures, polyneuropathy and hepatic dysfunction which should be coded as per CTCAE v5.0. 6. Health economic analysis to assess the cost-effectiveness of ciprofloxacin prophylaxis versus no prophylaxis for patients receiving induction therapy for ALL. Measured using patient records unless otherwise noted: 1. Rate of febrile episodes during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 2. Rate of febrile neutropenia during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 3. Rate of severe infection and infection-related deaths during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 4. Rates of AMR (antimicrobial resistance) measured from randomisation until end of trial declaration (approximately 10 years) measured using results from stool samples or peri-rectal swab cultures 5. Rate of antibiotic exposure during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 6. Rate of secondary infections during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 7. Quinolone side effects during induction, measured at approximately 1 month from randomisation until the start of consolidation, discontinuing protocol, antileukaemic therapy or death post induction 8. Cost-effectiveness of ciprofloxacin prophylaxis versus no prophylaxis - model-based health economic analysis measured using the EQ-5D (5L) questionnaire which is being collected on the ALL Together-1 study, on which the CiproPAL participants are enrolled |
| Overall study start date | 01/12/2020 |
| Completion date | 31/12/2031 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 1 Year |
| Upper age limit | 17 Years |
| Sex | Both |
| Target number of participants | 1,052 |
| Key inclusion criteria | Current participant inclusion criteria as of 10/01/2025: 1. Paediatric patients (1-17 years inclusive) with de-novo Acute Lymphoblastic Leukaemia treated on ALLTogether1 in the UK as soon as possible after commencing induction, preferably in the first 5-8 days of therapy, up to 14 days is acceptable. 2. Written informed consent. Previous participant inclusion criteria as of 15/11/2023 to 10/01/2025: 1. Paediatric patients (1 - 17 years inclusive) with de-novo acute lymphoblastic leukaemia treated on ALLTogether-1 in the UK in the first 14 days of therapy (but ideally day 5-8) 2. Written informed consent Previous participant inclusion criteria: 1. 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 2. Written informed consent |
| Key exclusion criteria | 1. Non-participants of the ALLTogether-1 trial 2. Patients with Down syndrome who already receive ciprofloxacin prophylaxis 3. Patients with chronic active arthritis 4. Other contraindication to fluoroquinolones |
| Date of first enrolment | 29/06/2022 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
London
NW1 2BU
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Manchester
M13 9WL
United Kingdom
Bristol
BS2 8BJ
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Liverpool
L12 2AP
United Kingdom
Southampton
SO16 6YD
United Kingdom
Leeds, West Yorkshire
LS1 3EX
United Kingdom
Sheffield
S10 2TH
United Kingdom
Derby Rd
Nottingham
NG7 2UH
United Kingdom
Edinburgh
EH9 1LF
United Kingdom
Leicester
LE1 5WW
United Kingdom
Aberdeen
AB25 2ZG
United Kingdom
London
WC1N 3JH
United Kingdom
Sponsor information
University/education
Joint Research Office
Gower Street
London
WC1E 6BT
England
United Kingdom
| Phone | +44 (0)207 3809995 |
|---|---|
| ctc.sponsor@ucl.ac.uk | |
| Website | https://www.ucl.ac.uk/joint-research-office/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Dissemination will be through academic outputs (papers, presentations, and reports) and connections with charities, patient and parent organisations, and international guideline groups. CiproPAL may change the management of children and young people with ALL across the UK and globally. |
| IPD sharing plan | Requests for de-identified data should be made in writing to the Trials Group Lead at the CR UK and UCL Cancer Trials Centre. Please see the UCL CTC website for access criteria and link to contact http://www.ctc.ucl.ac.uk/DataSampleSharing.aspx |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1 | 22/09/2021 | 15/12/2021 | No | No |
Additional files
Editorial Notes
12/05/2025: The recruitment end date was changed from 01/05/2025 to 31/12/2025.
15/01/2025: Ethics approval details added.
10/01/2025: The following changes were made:
1. IRAS number was amended from 293372 to 1004004.
2. NHS HRA ethics approval added.
3. Phase was added.
4. The secondary outcome measures were amended.
5. The participant inclusion criteria were amended.
6. The Royal Marsden Hospital, Birmingham Children’s Hospital, Noah’s Ark Children’s Hospital for Wales, Royal Hospital for Children and Royal Belfast Hospital for Sick Children were removed as study participating centres.
15/11/2023: The participant inclusion criteria were changed.
01/11/2023: The following changes were made:
1. Ethics approval was added.
2. The plain English summary was updated.
30/06/2022: The recruitment start date has been changed from 20/06/2022 to 29/06/2022.
25/05/2022: The recruitment start date has been changed from 20/05/2022 to 20/06/2022.
20/04/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/04/2022 to 20/05/2022.
2. The EudraCT number was added.
08/03/2022: The recruitment end date was changed from 01/03/2022 to 01/04/2022.
11/01/2022:The recruitment start date was changed from 01/01/2022 to 01/03/2022.
15/12/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/12/2021 to 01/01/2022.
2. The primary contact name was changed
3. Uploaded protocol (not peer-reviewed) as an additional file.
4. The plain English summary was updated to reflect these changes.
08/01/2021: Trial’s existence confirmed by National Institute for Health Research (NIHR)
