Condition category
Cancer
Date applied
21/11/2016
Date assigned
21/11/2016
Last edited
06/02/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 measures

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

29/12/2019

Reason abandoned

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

29/04/2018

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

31/07/2020

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

06/02/2017: Cancer Help UK lay summary link added to plain English summary field.