• Determine the safety profile, dose-limiting toxicity, and maximum tolerated dose of JNJ-26481585.
  

• Determine the pharmacokinetic profile of JNJ-26481585; Explore the pharmacodynamic effects and antitumor activity of JNJ-26481585.
  

JNJ-26481585, a histone deacetylase (HDAC) inhibitor, is a new drug in development for cancer. This research study is being carried out to determine what is the highest dose of JNJ-26481585 that patients with advanced or refractory leukemia or myelodysplastic syndrome can tolerate. The study will also test the safety (the effect on the body) of JNJ-26481585. JNJ-26481585 will be administered in a continuous regimen with 21-day treatment cycles. The dose of JNJ-26481585 will start low and will be increased during the study in groups of 2 to 6 patients. The dose each patient receives at study entry may be increased if deemed safe and desirable to optimize potential antitumor activity. If a group of patients does not have severe side effects, the next group of patients will get a higher dose. The dose will increase until some patients have severe side effects. The dose will then be decreased to a dose level where severe side effects are observed in less than 1/3 of patients. Once a safe dose level has been determined an additional group of 16 patients will be treated. The amount of JNJ-26481585 in the blood will be measured and the effect on the disease will be evaluated in all patients. Patients will be screened for eligibility within 4 weeks before study treatment is given. The treatment will consist of 21-day treatment cycles in a continuous once daily dosing regimen. The duration of treatment will depend on adverse effects and whether there is benefit from the treatment. The design of a cycle may be adjusted during the course of the study to include days when there is no treatment (a pause) as guided by clinical observations. Patients will be informed if there are changes in the design of a cycle. During the first treatment cycle, patients are required to stay in the hospital for 2 or 3 nights. In addition there are 8 daytime visits during Cycles 1 and 2 (combined) that may take up to 12 hours after the morning dose at 2 occasions and up to 4 hours after the morning dose at the other 6 occasions. From Cycle 3 onwards, there is only 1 daytime visit per treatment cycle, and these visits usually take up less time. Throughout the study, especially during Cycles 1 and 2, patients will undergo frequent blood and urine tests, procedures to assess safety including heart function, and tests to assess the course of the patient's illness. Two weeks after the last dose of the study drug, patients are required to return to the study site for follow-up assessments.

JNJ-26481585 will be provided as capsules and will be taken by mouth once daily throughout treatment. The dose received by an individual patient will be determined at the time of enrollment. Modifications to the treatment schedule or dosing regimen may be explored during the course of this study. Patients can continue receiving treatment as long as there is benefit as evaluated by the study doctor and there are no unacceptable side effects.