Randomised Study of Azacitidine Versus Azacitidine With Vorinostat in Patients With AML or High Risk MDS (RAvVA)
Leukemia, Myeloid, Acute
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
Inclusion Criteria:
- Adults with AML (except Acute Promyelocytic Leukaemia (APL)) as defined by the World Health Organisation (WHO) Classification or patients with high risk MDS categorised as INT-2 or high risk according to the International Prognostic Scoring System (IPSS) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities with ONE of the following disease status:- i) Newly diagnosed OR
ii) Relapsed Disease: patients must have achieved a previous morphological CR and show evidence of recurrent disease OR
iii) Refractory Disease: patients who have failed to achieve a morphological CR with previous therapy
- Patients are able to receive treatment as out-patient
- Adequate renal and hepatic function as defined in the Protocol
- Patients have given written informed consent
- ECOG performance status less than or equal to 2
Exclusion Criteria:
- Patients with greater than class III NYHA cardiac impairment
- Blastic transformation of Chronic Myeloid Leukaemia
- Prior allogeneic/autologous haematopoietic stem cell transplant
- Pregnant or lactating women
- Adults of reproductive potential not willing to use appropriate, effective, contraception during the trial and for specified amount of time afterwards
- Patients who have received prior histone deacetylase inhibitor (HDACi) treatment as anti-tumour therapy. (Patients who have received HDACi treatment for other indications e.g valproic acid for epilepsy may enrol after a 30-day washout period)
- Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 30 days before the start of protocol treatment. (Patients receiving anti-tumour therapies to control blood counts may enrol into the trial)
- Patients who have received prior treatment with demethylating agents such as 5-azacitidine or decitabine
- Patients with contraindications to receiving azacitidine or vorinostat such as hypersensitivity, patients unable to have a subcutaneous injection or swallow oral capsules
- Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis
- Any co-morbidity that could limit compliance with the trial
Sites / Locations
- Barts and the London NHS Trust
- King's College Hospital
- Hammersmith Hospital
- The Christie Hospital
- Royal Liverpool University Hospital
- Belfast City Hospital
- Nottingham University Hospitals NHS Trust
- Oxford University Hospitals NHS Trust
- University Hospital of Wales
- Queen Elizabeth Hospital
- St James's University Hospital
- Beatson West of Scotland Cancer Centre
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
azacitidine
azacitidine and vorinostat
azacitidine (75mg/m2) by SC injection on 7 consecutive days (excluding weekends), starting day 1 of 28-day cycles for up to 6 cycles. This should be delivered in a 5-2-2 schedule
Patients will receive (75mg/m2) azacitidine by SC injection on 7 consecutive days (excluding weekends), starting day 1 of 28-day cycles for up to 6 cycles. Azacitidine should be delivered in a 5-2-2 schedule. Vorinostat (300mg bid) will be taken orally for 7 consecutive days starting on day 3 of each cycle in 28-day cycles for up to 6 cycles. (Day 3 is defined as the 3rd day of azacitidine administration).