Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
This phase I trial is studying the side effects and best dose of decitabine and valproic acid in treating patients with refractory or relapsed acute myeloid leukemia or previously treated chronic lymphocytic leukemia or small lymphocytic leukemia. Drugs used in chemotherapy, such as decitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Valproic acid may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Combining decitabine with valproic acid may kill more cancer cells.
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Recurrent Adult Acute Myeloid Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: valproic acid
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Selected Hematologic Malignancies|
- MEPD of single agent decitabine [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- MTD of the combination of valproic acid with the MEPD of decitabine [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]
- MEPD of valproic acid in combination with decitabine [ Time Frame: Up to 29 days ] [ Designated as safety issue: Yes ]
- Qualitative and quantitative toxicities of single agent decitabine alone and in combination with valproic acid in regard to organ specificity, time course, predictability, and reversibility [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2004|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (decitabine, valproic acid)
Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days.
Cohorts of 6 patients receive escalating doses of decitabine until the MEPD is determined. The MEPD is defined as the dose at which at least 5 of 6 patients meet gene methylation criteria and no more than 1 of 6 patients experiences DLT.
Once the MEPD is determined, patients receive decitabine at that dose level administered as above and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days.
Cohorts of 3-6 patients receive escalating doses of valproic acid until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. The MEPD of valproic acid is then determined using established gene methylation and toxicity criteria. Treatment continues for up to 24 months in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: valproic acid
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079378
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Kristie Blum||Ohio State University|