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

Completed

Conditions: Acute myeloid leukaemia or high risk myelodysplasia
Cancer
Leukamia

Registration Number: ISRCTN68418952

Lead Sponsor: niversity of Birmingham (UK)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 20

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Assessment of safety of the four drugs sodium valproate, 5-azacitidine, theophylline and ATRA when administered in combination<br>2. Haematological responses to sodium valproate, 5-azacitidine, theophylline and ATRA when administered in combination

Secondary Outcome Measures

Name	Time	Method
1. To assess the impact of the combined therapy on measures of apoptosis and differentiation<br>2. To assess the impact of the combined therapy on the chromatin structure of blast cell population