Phase II study of the tolerability and efficacy of the histone deacetylase inhibitor sodium valproate administered in conjunction with 5-azacitidine, theophylline and all trans-retinoic acid in patients with acute myeloid leukaemia and high risk myelodysplasia

ISRCTN ISRCTN68418952
DOI https://doi.org/10.1186/ISRCTN68418952
Secondary identifying numbers HM2009
Submission date
21/08/2006
Registration date
05/10/2006
Last edited
09/05/2012
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

Not provided at time of registration

Contact information

Prof Charles Craddock
Scientific

Queen Elizabeth Hospital
Centre for Clinical Haematology
Edgbaston
Birmingham
B15 2TH
United Kingdom

Study information

Study designPhase II, multi-centre, open label, non-randomised study
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study acronymVal/Aza
Study objectivesThe 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(s)West Midlands multi-centre Research Ethics Committee (reference 05/MRE07/74).
Health condition(s) or problem(s) studiedAcute myeloid leukaemia or high risk myelodysplasia
InterventionPatients will receive combination therapy with sodium valproate, 5-azacitidine, theophylline and ATRA for the duration of the study (85 days).
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Sodium valproate, 5-azacitidine, theophylline and all trans-retinoic acid.
Primary outcome measure1. 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 measures1. 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 study start date22/06/2006
Completion date01/06/2008

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants20
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment22/06/2006
Date of final enrolment01/06/2008

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Website http://www.bham.ac.uk
ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Industry

Pharmion Ltd (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 16/09/2010 Yes No