Azacytidine With Valproic Acid Versus Ara-C in Acute Myeloid Leukemia (AML)/ Myelodysplastic Syndrome (MDS) Patients
1. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age > or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents.
1. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.
|Acute Myelogenous Leukemia Myelodysplastic Syndrome Leukemia||Drug: 5-Azacytidine Drug: Ara-C Drug: Valproic Acid (VPA)||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies|
- Number of Participants With Response [ Time Frame: Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end ]Patient response defined by: Death, Resistant to Therapy [no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses], or Relapse.
|Study Start Date:||August 2005|
|Study Completion Date:||February 2008|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 5-Aza + VPA
5-Azacytidine (5-Aza) 75 mg/m^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m^2 orally daily, each for 7 days
75 mg/m^2 daily for 7 days (days 1-7) via subcutaneous injection.
Other Names:Drug: Valproic Acid (VPA)
50 mg/m^2 orally daily days 1-7.
Active Comparator: Ara-C
Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days.
20 mg twice daily via subcutaneous injection for 10 days.
5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard of care for the treatment of leukemia and MDS in older patients not eligible for other therapies.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first, there will be an equal chance of being assigned to either group. As the study goes along, however, the chance of being assigned to the treatment that has worked best so far will increase.
Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin once a day for 7 days in a row. On these same 7 days, participants in this group will also take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be repeated every 4 to 6 weeks.
Participants in the ara-C group will receive ara-c twice a day as an injection under the skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks.
You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a week during this study.
You may receive up to 12 cycles of therapy. You may be taken off study early if the disease gets worse or intolerable side effects occur.
Once you go off study, you will have standard follow-up as is required by your primary physician.
This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved for acute myelogenous leukemia. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00382590
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Guillermo Garcia-Manero, MD||M.D. Anderson Cancer Center|