Clinical trial NCT00948064
Conditions: Leukemia
Keywords: Leukemia Acute Myelogenous Leukemia AML Myelodysplastic Syndrome MDS Vorinostat SAHA Suberoylanilide Hydroxamic Acid MSK-390 Zolinza Azacitidine 5-Azacitidine 5-Aza Vidaza 5-AZC AZA-CR Ladakamycin NSC-102816
Sponsor: M.D. Anderson Cancer Center
Start date: 2009-09-08; Completion date: 2017-08-03
Enrollment: 110 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this clinical research study is to learn if the combination of azacitidine and vorinostat can help to control AML or MDS better than azacitidine alone. The safety of this drug combination will also be studied.

Detailed description:
The Study Drugs:

Azacitidine is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes may be able to work better.

Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.

* If you are in Group 1, you will receive azacitidine and vorinostat.
* If you are in Group 2, you will receive azacitidine alone.

For the first 40 patients, you will have an equal chance of being in either group. After the first 40 patients, you will have a higher chance of being assigned to a group based on the results from previous participants.

Study Drug Administration:

On Days 1-5 of every cycle, you will receive azacitidine by vein over 15-30 minutes.

If you are in Group 1, you will also take vorinostat by mouth 3 times a day with food on Days 1-5 of every cycle.

If you cannot take vorinostat by mouth during a cycle, you will receive only azacitidine during that cycle. You will begin taking vorinostat by mouth again when you are able.

Your dose of study drugs may be lowered if you experience side effects.

You may receive a drug such as ondansetron before each dose of azacitidine to prevent nausea and vomiting.

If you have diarrhea, you will take a drug such as Imodium (loperamide) to prevent diarrhea.

Study Visits:

Once a week of Cycle 1, the following tests and procedures will be performed:

* Your complete medical history will be recorded.
* You will have a physical exam.
* You will be asked if you have experienced any intolerable side effects.
* Blood (about 1-2 tablespoons) will be drawn for routine tests.

On Day 28 of Cycle 1 (+/- 3 days), you will have bone marrow aspiration to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

If the doctor thinks it is needed, you will have extra bone marrow aspirations during the later cycles to check the status of the disease.

One (1) time each cycle of Cycles 2 and beyond, the following tests and procedures will be performed:

* Your complete medical history will be recorded.
* You will have a physical exam.
* You will be asked if you have experienced any intolerable side effects.
* If the doctor thinks it is needed, blood (about 2 tablespoons) will be drawn for routine tests.

Length of Study:

You will be on active study for up to 12 cycles (about 12-18 months). You will be taken off study if the disease gets worse or you experience intolerable side effects.

This is an investigational study. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. Azacitidine is FDA approved commercially available for the treatment of MDS. The combination of these drugs for use in patients with intermediate-1 or higher risk MDS and AML is investigational.

Up to 80 participants will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks. arm 2: ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Interventions: intervention 1: Vorinostat intervention 2: Azacitidine
Intervention descriptions: intervention 1: 200 mg by mouth three (3) times per day with food for 5 days (Days 1 - 5) intervention 2: 75 mg/m\^2/day given intravenously over 15 - 30 minutes daily for 5 days (Days 1 - 5)

Protocol documents: