Contact information
Type
Scientific
Primary contact
Dr Andrea Hodgkinson
ORCID ID
Contact details
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
+44 121 371 4365
a.hodgkinson@bham.ac.uk
Additional identifiers
EudraCT number
2014-005659-19
ClinicalTrials.gov number
Protocol/serial number
19722
Study information
Scientific title
A phase II study of the use of azacitidine for the treatment of patientswith chronic graft-versus-host-disease who have failed therapy with corticosteroids
Acronym
AZTEC
Study hypothesis
The aim of this study is to determine the value of azacitidine in patients with chronic graft-versus-host-disease (GvHD) who do not respond to, or have become dependent on, steroids.
Ethics approval
East Midlands- Nottingham 2 Research Ethics Committee, 21/10/2015, ref: 15/EM/044
Study design
Non-randomised; Interventional; Design type: Treatment, Drug
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
See additional files
Condition
Specialty: Cancer, Primary sub-specialty: Haematological Oncology
Intervention
All patients will receive treatment with 36mg/m2 of azacitidine of days 1-5 of each cycle. Each cycle will last 28 days. Azacitidine may be administered via subcutaneous injection or intravenously. Patients will receive 6 cycles of azacitidine treatment. Patients may continue beyond 6 cycles (maximum of 10) if clinical benefit is observed. The patients will be followed up for 6 months after the last treatment with azacitidine. The maximum duration the patient will be on study is 16 months.
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Best overall response (complete or partial) (GvHD) within 6 months as defined by modified National Institutes of health (NIH) Consensus Response Criteria – analysed by the number and proportion of patients in each response category (GvHD) reported within 6 months and overall, as a proportion of the total number of patients recruited with 95% confidence intervals.
Secondary outcome measures
1. Best organ level response (GvHD) as determined by the incremental improvement and changes in individual organ systems involved in cGvHD according to modified NIH Consensus Response Criteria – analysed by the number of patients in each clinical response category (GvHD) based on their overall ‘best’ response and changes in the patients’ organ systems will be reported and presented as a proportion of the total number of patients recruited with 95% confidence intervals within 6 months
2. Quality of Life is measured using the FACT-BMT (version 4) questionnaire at baseline, cycles 1-6 and if clinical response seen cycles 7-10, end of treatment visit and 3 and 6 month follow-up
3. Duration of response measured via average duration of response reported with full range and Reduction in corticosteroid dosage – analysed by the percentage change from baseline in corticosteroid dosage at 6 months and one year
Overall trial start date
21/12/2012
Overall trial end date
29/12/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients with moderate or severe cGvHD OR progressive, recurrent or delayedonset acute GvHD as defined by the NIH Consensus Conference Diagnostic Criteria who have failed therapy with corticosteroids (+/ calcineurin inhibitors).
Failure of corticosteroid is defined as either:
1.1. Progression of cGvHD on 1mg/kg/day prednisolone over 2 weeks
1.2. Stable cGvHD on ≥0.5mg/kg/day prednisolone over 4 weeks
1.3. Inability to taper prednisolone below 0.5mg/kg/day without recurrence of clinical manifestations
1.4. Inability to tolerate first line therapy* (eg steroid myopathy, calcineurin inhibitorinduced renal toxicity)
*Patients must have proven steroid toxicity to meet this criterion for having failed corticosteroid therapy. These cases must be discussed with the Chief Investigator prior to trial entry.
2. Patients must be unable to receive treatment with extracorporeal photophoresis (ECP) therapy (either refractory/intolerant to ECP, lack of ECP availability at local institution or patient/physician preference)
3. Age ≥16 years of age
4. Life expectancy of at least 3 months with no imminent relapse expected
5. Women of childbearing potential and all men must be using adequate birth control measures throughout the study and for a minimum of 3 months following the end of trial treatment
6. Able to provide written informed consent
7. Patients must be able to comply with all study procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 35; UK Sample Size: 35
Participant exclusion criteria
1. Uncontrolled infection ≥ grade 3 requiring treatment at study entry
2. Neutrophil count <1x109/L (support with GCSF permitted)
3. Platelet count <30 x109/L
4. Known HIV infection
5. Known hepatitis B or C
6. ECOG ≥ 3
7. Patients with ocular GvHD only
8. Pulmonary GvHD
9. Patients receiving active therapy for cGvHD within 14 days of study entry (with the exception of corticosteroids and calcineurin inhibitors)
10. Any investigational agents within 14 days of study entry
11. Treatment with ECP within 6 months of study entry
12. Known hypersensitivity to azacitidine
13. Women who are pregnant or breastfeeding
14. Any other condition that in the Investigator's opinion will affect the patient's participation in this trial
Recruitment start date
29/04/2016
Recruitment end date
31/08/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Bartholomew’s Hospital
West Smithfield
London
EC1A 7DE
United Kingdom
Trial participating centre
Bristol Haematology & Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Trial participating centre
Cambridge Cancer Trials Centre
Cambridge University Hospitals NHS Foundation Trust
Addenbrooke’s Hospital
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
Trial participating centre
Freeman Hospital
Freeman Road
High Heaton
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
Trial participating centre
St Marys Hospital
Praed Street
London
W2 1NY
United Kingdom
Trial participating centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Trial participating centre
St James University Hospital
Becket Street
Leeds
LS9 7TF
United Kingdom
Trial participating centre
University Hospital Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Research Support Group
Aston Webb
B Block
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 1214 158011
researchgovernance@contacts.bham.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Leukaemia and Lymphoma Research
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The results of this trial will be submitted for publication in a peer reviewed journal. This would be at the end of the follow-up period (December 2019). Short communications and abstracts may be prepared during the earlier parts of the study depending on the data collected.
IPD Sharing plan:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.
Intention to publish date
31/07/2021
Participant level data
Other
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN15649711_PIS_07Oct15_V2.0.pdf Uploaded 21/11/2016