Trial Information

A Phase 1 Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Subjects With Advanced or Refractory Leukemia or Myelodysplastic Syndrome

This is an open-label (all people know the identity of the intervention), Phase 1 dose
escalation, 2-part study (Part I and Part II). In Part I of the study, the Maximum Tolerated
Dose (MTD) defined as the highest dose with an observed incidence of dose limiting toxicity
(DLT) in no more than 1 in 6 patients, will be determined using rapid escalation (Stage 1)
followed by conventional escalation (Stage 2). In Stage 1, at least 2 patients will be
enrolled at each dose level; dose increments of 100% will be applied. In Stage 2, at least 3
patients will be enrolled at each dose level and dose increments of 20-50% will be
implemented. Decisions on dose escalation or de-escalation, changes in the timing of
pharmacokinetic/pharmacodynamic sampling, and the exploration of an alternative schedule
were to be made by the Study Evaluation Team (SET), which consisted of all principal
investigators, the medical monitor, and 1 of the sponsor's clinical pharmacologists. Part II
of the study will be the expansion phase, which will begin after the MTD had been determined
in Part I and an additional cohort of patients with MDS will be enrolled to further explore
the safety and activity of JNJ 26481585 in patients with MDS. The starting dose for patients
enrolled in Part II of the study was to be the MTD established in Part I. Depending on the
outcome, the SET may decide to continue at the MTD dose, or dose-de-escalate to the next
lower level (25 50% decrement from MTD). The cohort for MDS will be expanded to consist of
16 evaluable patients. Safety will be evaluated throughout the study and will include
evaluations of adverse events clinical laboratory tests, electrocardiogram (ECG), vital
signs, 24 hours Holter ECG, physical examination, Eastern Cooperative Oncology Group
performance status and Multiple Gated Acquisition scan or echocardiography.