A phase II study of the use of azacitidine for the treatment of patients with chronic graft-versus-host-disease
- Conditions
- Chronic graft-versus-host-diseaseCancer
- Registration Number
- ISRCTN15649711
- Lead Sponsor
- niversity of Birmingham
- Brief Summary
2021 Interim results article in https://pubmed.ncbi.nlm.nih.gov/34446853 Results of first stage (tolerability) of two-stage study (added 18/12/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 14
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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<br>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 <br>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