5-Azacitidine versus 5-Azacitidine in combination with Vorinostat in patients with relapsed acute myeloid leukaemia ineligible for intensive chemotherapy
| ISRCTN | ISRCTN68224706 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68224706 |
| EudraCT/CTIS number | 2011-005207-32 |
| ClinicalTrials.gov number | NCT01617226 |
| Secondary identifying numbers | 12452 |
- Submission date
- 29/06/2012
- Registration date
- 29/06/2012
- Last edited
- 19/05/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Miss Nadira Jilani
Scientific
Scientific
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
| n.y.jilani@bham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Phase II randomised trial of 5-Azacitidine versus 5-Azacitidine in combination with Vorinostat in patients with relapsed acute myeloid leukaemia ineligible for intensive chemotherapy |
| Study acronym | RAvVA |
| Study objectives | This is a multicentre, open-label randomised phase II trial, comparing azacitidine monotherapy with combined azacitidine and vorinostat in patients with relapsed Acute Myeloid Leukaemia (AML). |
| Ethics approval(s) | NRES West Midlands Research Ethics Committee, 12/WM/0087; First MREC approval date 21/05/2012 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid) |
| Intervention | Patients will be randomised on 1:1 ratio to treatment. It is anticipated 80 patients will be randomised to receive azacitidine monotherapy and 80 patients will be randomised to receive azacitidine and vorinostat, combined therapy. Azacitidine, azacitidine (75 mg/m2) subcutaneous (s.c.) x 7 per cycle on days 1-5, 8, 9 of each 28-day cycle Azacitidine + vorinostat: Azacitidine (75 mg/m2) s.c. x 7 per cycle on days 1-5, 8, 9 of each 28-day cycle Vorinostat (300mg) twice a day (bid) x 7 per cycle on days 3-9 of each 28-day cycle Follow Up Length: 24 month(s) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | 5-Azacitidine, Vorinostat |
| Primary outcome measure | Overall Response Rate assessed within 6 cycles of treatment |
| Secondary outcome measures | Overall Survival from randomisation until 24 months |
| Overall study start date | 01/09/2012 |
| Completion date | 01/09/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 160; UK Sample Size: 160 |
| Total final enrolment | 259 |
| Key inclusion criteria | 1. Adults with AML in first relapse (except Acute Promyelocytic Leukaemia (APL) as defined by the World Health Organisation (WHO) Classification) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities 2. Patients must have achieved a previous morphological complete response (CR) as defined by Cheson criteria after treatment with conventional myelosuppressive chemotherapy e.g. anthracycline, araC, etoposide containing regimens 3. Patients are able to receive treatment as an outpatient 4. Adequate renal and hepatic function 5. Patients have given written informed consent 6. Eastern Cooperative Oncology Group (ECOG) performance status <=2 7. Male & Female; Lower Age Limit 18 years |
| Key exclusion criteria | 1. Patients with greater than class III of the New York Heart Association (NYHA) cardiac impairment 2. Blastic transformation of Chronic Myeloid Leukaemia (CML) 3. Any concurrent active malignancy 4. Prior allogeneic/autologous haematopoietic stem cell transplant (HSCT) 5. Pregnant or lactating women (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the start of treatment) 6. Adults of reproductive potential not willing to use appropriate medically approved contraception during the trial and for specified amount of time afterwards. 7. Patients who have received prior HDAC inhibitor-like 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). 8. Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 30 days before 9. Patients who have received prior treatment with demethylating agents such as 5azacitidine or decitabine 10. Patients with contraindications to receiving azacitidine or vorinostat such as hypersenstivity or patients unable to receive subcutaneous injection 11. Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis 12. Any co-morbidity that could limit compliance with the trial |
| Date of first enrolment | 01/09/2012 |
| Date of final enrolment | 01/09/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Charity
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Basic results | 11/01/2022 | 19/05/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
19/05/2022: EU Clinical Trials Register results added.
25/04/2019: The following changes were made to the trial record:
1. Link to plain English results added to: Results (plain English).
2. The total final enrolment was added.
16/11/2016: No publications found, verifying study status with principal investigator.
