Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HM2009
Study information
Scientific title
Acronym
Val/Aza
Study hypothesis
The purpose of this study is to assess the tolerability and anti-leukaemic activity of four drugs, sodium valproate, 5-azacitidine, theophylline and All Trans-Retinoic Acid (ATRA) when administered in combination to patients with Acute Myeloid Leukaemia (AML) or high risk Myelodysplasia (MDS). All four drugs have been shown to have anti-leukaemic activity in vitro but their combined use has not been studied clinically in patients with leukaemia. This study will also analyse the impact of these agents on biochemical measures of chromatin structure and cellular differentiation permitting correlation of these parameters with clinical activity of these drugs in AML and high risk MDS.
Ethics approval
West Midlands multi-centre Research Ethics Committee (reference 05/MRE07/74).
Study design
Phase II, multi-centre, open label, non-randomised study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Acute myeloid leukaemia or high risk myelodysplasia
Intervention
Patients will receive combination therapy with sodium valproate, 5-azacitidine, theophylline and ATRA for the duration of the study (85 days).
Intervention type
Drug
Phase
Phase II
Drug names
Sodium valproate, 5-azacitidine, theophylline and all trans-retinoic acid.
Primary outcome measure
1. Assessment of safety of the four drugs sodium valproate, 5-azacitidine, theophylline and ATRA when administered in combination
2. Haematological responses to sodium valproate, 5-azacitidine, theophylline and ATRA when administered in combination
Secondary outcome measures
1. To assess the impact of the combined therapy on measures of apoptosis and differentiation
2. To assess the impact of the combined therapy on the chromatin structure of blast cell population
Overall trial start date
22/06/2006
Overall trial end date
01/06/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients satisfying World Health Organisation (WHO) criteria for diagnosis of AML or high risk MDS
2. Relapsed or refractory AML who are considered unfit for intensive chemotherapy
3. Patients with de novo AML who are either older than 70 years, or between 60 and 69 years of age with a history of cardiac disease
4. Patients with high risk MDS judged to be ineligible for intensive chemotherapy or stem cell transplantation
5. Age equal or greater than 18 years
6. WHO performance status of zero to two
7. Patients must be able to swallow capsules
8. At least two weeks from previous chemotherapy
9. Patients with White Blood Cell (WBC) count of more than 15 x 10^9/L may receive Hydroxyurea in order to keep the WBC less than 10 x 10^9/L
10. All men and women must agree to practice effective contraception during the entire study period
11. All women of child bearing potential must have a negative pregnancy test
12. Aspartate transaminase less than or equal to 2.5 x the Upper Limit of Normal (ULN)
13. Total bilirubin less than or equal to 2.5 x the ULN
14. Calculated creatinine clearance more than or equal to 50 mL/minute
15. Written informed consent, and the ability of the patient to co-operate with treatment and follow up must be ensured and documented
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20
Participant exclusion criteria
1. Patients with contraindications to receiving sodium valproate, ATRA or 5-azacitidine will be excluded from the study. Contraindications are detailed as follows:
a. sodium valproate - hypersensitivity to sodium valproate, acute liver disease, family history of severe hepatic dysfunction, porphyria, history of pancreatitis, active systemic lupus erythematosis
b. ATRA - hypersensitivity to ATRA
c. 5-azacitidine - hypersensitivity to 5-azacitidine
d. history of sensitivity to theophylline
2. Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection
3. Patients with any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial
4. Pregnant or lactacting women
5. Patients known to be serologically positive for Hepatitis B, C or Human Immunodeficiency Virus (HIV)
6. Concurrent congestive heart failure or prior history of New York Heart Association class III/IV cardiac disease
Recruitment start date
22/06/2006
Recruitment end date
01/06/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Pharmion Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20530795
Publication citations
-
Results
Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, Vyas P, Cavenagh J, Stankovic T, Moss P, Craddock C, Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia., Blood, 2010, 116, 11, 1908-1918, doi: 10.1182/blood-2009-11-249474.