Chronic Graft versus Host Disease MedDRA version: 18.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Vidaza
Product Name: Azacitidine
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Azacitidine
CAS Number: 320672
Current Sponsor code: Azaci
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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: o progression of cGvHD on 1mg/kg/day prednisolone over 2 weeks o stable cGvHD on =0.5mg/kg/day prednisolone over 4 weeks o inability to taper prednisolone below 0.5mg/kg/day without recurrence of clinical manifestations o inability to tolerate first line therapy* (eg steroid myopathy, calcineurin inhibitor-induced 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. • 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) • Age =16 years of age • Life expectancy of at least 3 months with no imminent relapse expected • 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 • Able to provide written informed consent • Patients must be able to comply with all study procedures Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: • Uncontrolled infection = grade 3 requiring treatment at study entry • Neutrophil count <1x109/L (support with GCSF permitted) • Platelet count <30 x109/L • Known HIV infection • Known hepatitis B or C • ECOG = 3 • Patients with ocular GvHD only • Pulmonary GvHD • Patients receiving active therapy for cGvHD within 14 days of study entry (with the exception of corticosteroids and calcineurin inhibitors) • Any investigational agents within 14 days of study entry • Treatment with ECP within 6 months of study entry • Known hypersensitivity to azacitidine • Women who are pregnant or breastfeeding • Any other condition that in the Investigator's opinion will affect the patient's participation in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and activity (in terms of best overall response within 6 months) of azacitidine in the treatment of patients with cGVHD who have failed therapy with corticosteroids;Secondary Objective: • Best organ level response as determined by improvement and changes in individual organ systems involved in cGvHD • Proportion of patients with a mixed response • Quality of Life (QoL) • Duration of response • Reduction in the dose of corticosteroids ;Primary end point(s): Best overall response (complete or partial) (GvHD) within 6 months as defined by modified National Institutes of Health (NIH) Consensus Response Criteria Tolerability of azacitidine defined as the absence of grade 3 or 4 clinically relevant and drug related adverse events (AEs) resulting in stopping treatment early including treatment related deaths within 6 months;Timepoint(s) of evaluation of this end point: Within 6 cycles of trial treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 Proportion of patients with mixed response as defined by modified National Institutes of Health (NIH) Consensus Response Criteria Quality of Life (QoL) Duration of response Reduction in corticosteroid dosage ;Timepoint(s) of evaluation of this end point: Following 6 cycles of treatment. | — |
Countries
United Kingdom
Contacts
Public ContactSonia Fox
University of Birmingham
Outcome results
None listed