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 |
| Protocol serial number | HM2009 |
| Sponsor | University of Birmingham (UK) |
| Funder | Pharmion Ltd (UK) |
- 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
Scientific
Queen Elizabeth Hospital
Centre for Clinical Haematology
Edgbaston
Birmingham
B15 2TH
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase II, multi-centre, open label, non-randomised study |
| Secondary study design | Non randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | |
| Study acronym | Val/Aza |
| Study objectives | 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(s) | West Midlands multi-centre Research Ethics Committee (reference 05/MRE07/74). |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Sodium valproate, 5-azacitidine, theophylline and all trans-retinoic acid. |
| Primary outcome measure(s) |
1. Assessment of safety of the four drugs sodium valproate, 5-azacitidine, theophylline and ATRA when administered in combination |
| Key secondary outcome measure(s) |
1. To assess the impact of the combined therapy on measures of apoptosis and differentiation |
| Completion date | 01/06/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 20 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 22/06/2006 |
| Date of final enrolment | 01/06/2008 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not 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 | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
