A phase II study of the use of azacitidine for the treatment of patients with chronic graft-versus-host-disease

ISRCTN	ISRCTN15649711
DOI	https://doi.org/10.1186/ISRCTN15649711
EudraCT/CTIS number	2014-005659-19
Secondary identifying numbers	19722

Submission date: 21/11/2016
Registration date: 21/11/2016
Last edited: 18/12/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-using-azacitidine-for-people-with-chronic-graft-versus-host-disease-aztec

Study website

Contact information

Dr Andrea Hodgkinson
Scientific

Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Phone	+44 (0)121 371 4365
Email	a.hodgkinson@bham.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Treatment, Drug
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	ISRCTN15649711_PIS_07Oct15_V2.0.pdf
Scientific title	A phase II study of the use of azacitidine for the treatment of patients with chronic graft-versus-host-disease who have failed therapy with corticosteroids
Study acronym	AZTEC
Study objectives	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(s)	East Midlands- Nottingham 2 Research Ethics Committee, 21/10/2015, ref: 15/EM/044
Health condition(s) or problem(s) studied	Chronic graft-versus-host-disease
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
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 study start date	21/12/2012
Completion date	29/12/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Sex	Both
Target number of participants	Planned Sample Size: 35; UK Sample Size: 35
Total final enrolment	14
Key inclusion criteria	1. Patients with moderate or severe cGvHD OR progressive, recurrent or delayed onset 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 1 mg/kg/day prednisolone over 2 weeks 1.2. Stable cGvHD on ≥0.5 mg/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
Key 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
Date of first enrolment	29/04/2016
Date of final enrolment	31/12/2019

Locations

Countries of recruitment

England
United Kingdom
Wales

Study participating centres

St Bartholomew’s Hospital

West Smithfield
London
EC1A 7DE
United Kingdom

Bristol Haematology & Oncology Centre

Horfield Road
Bristol
BS2 8ED
United Kingdom

Cambridge Cancer Trials Centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrooke’s Hospital
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Churchill Hospital

Old Road
Headington
Oxford
OX3 7LJ
United Kingdom

Freeman Hospital

Freeman Road
High Heaton
Newcastle-upon-Tyne
NE7 7DN
United Kingdom

St Marys Hospital

Praed Street
London
W2 1NY
United Kingdom

Manchester Royal Infirmary

Oxford Road
Manchester
M13 9WL
United Kingdom

Queen Elizabeth Hospital

Edgbaston
Birmingham
B15 2TH
United Kingdom

Royal Liverpool Hospital

Prescot Street
Liverpool
L7 8XP
United Kingdom

St James University Hospital

Becket Street
Leeds
LS9 7TF
United Kingdom

University Hospital Wales

Heath Park
Cardiff
CF14 4XW
United Kingdom

Sponsor information

University of Birmingham
University/education

Research Support Group
Aston Webb, B Block
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Phone	+44 (0)1214 158011
Email	researchgovernance@contacts.bham.ac.uk
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Charity

Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Results and Publications

Intention to publish date	29/12/2023
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	version V2.0	07/10/2015	21/11/2016	No	Yes
Plain English results			04/05/2022	No	Yes
Interim results article	Results of first stage (tolerability) of two-stage study	01/12/2021	18/12/2023	Yes	No

Additional files

ISRCTN15649711_PIS_07Oct15_V2.0.pdf: Uploaded 21/11/2016

Editorial Notes

18/12/2023: Publication reference added.
04/05/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
20/09/2021: Internal review.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Haematological Oncology" to "Chronic graft-versus-host-disease" following a request from the NIHR.
04/10/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/08/2018 to 31/12/2019.
2. The overall trial end date was changed from 29/12/2020 to 29/12/2022.
3. The intention to publish date was changed from 31/07/2021 to 29/12/2023.
08/08/2018: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 29/12/2019 to 29/12/2020
2. The recruitment end date has been changed from 29/04/2018 to 31/08/2018
3. The intention to publish date has been changed from 31/07/2020 to 31/07/2021
06/02/2017: Cancer Help UK lay summary link added to plain English summary field.