Phase I/II Study of Decitabine and Valproic Acid in Relapsed/Refractory Leukemia or Myelodysplastic Syndromes
Drug: Valproic acid
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of 5-aza-2'-Deoxycytidine and Valproic Acid in Patients With Relapsed/Refractory Leukemia or Myelodysplastic Syndromes|
- Maximum Tolerated Dose (MTD) of Valproic Acid + Decitabine [ Time Frame: Up to 8 weeks of therapy ] [ Designated as safety issue: Yes ]MTD is the dose level at which less than two participants develop a dose limiting toxicity (DLT). Response evaluated after completing first cycle, 4-8 weeks of therapy.
|Study Start Date:||January 2004|
|Study Completion Date:||November 2006|
|Primary Completion Date:||March 2005 (Final data collection date for primary outcome measure)|
Experimental: Decitabine + Valproic acid
Decitabine 15 mg/m^2 by vein over 1 hour times 10 days
15 mg/m^2 by vein over 1 hour times 10 days
Other Name: Dacogen®Drug: Valproic acid
20 mg/kg given orally daily for 10 days
Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. It has been shown that both DNA methylation and histone deacetylation work together in affecting gene expression.
Therefore, drugs that inhibit DNA methylation and those that inhibit histone deacetylase can reactivate silenced genes in combination better than they can individually. Decitabine (5 aza-2'deoxycytidine), a drug that produces marked DNA hypomethylator, has demonstrated antileukemic activity at low doses. There are several drugs that have been shown to have histone acetylase activity. One of these is valproic acid that has been used safely for many years as an anti-seizure medication.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00075010
|United States, Texas|
|M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Guillermo Garcia-Manero, M.D.||M.D. Anderson Cancer Center|