Condition category
Cancer
Date applied
21/08/2006
Date assigned
05/10/2006
Last edited
09/05/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Charles Craddock

ORCID ID

Contact details

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

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 measures

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

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

http://www.bham.ac.uk

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

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20530795

Publication citations

  1. 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.

Additional files

Editorial Notes