A Dose Escalation Study of the Histone Deacetylase Inhibitor (HDACi) JNJ 26481585 in Combination With VELCADE (Bortezomib) and Dexamethasone for Patients With Relapsed Multiple Myeloma

• Determine the dose-limiting toxicity and set the MTD for the combination of JNJ-26481585 and VELCADE-dexamethasone [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  Based on the safety analysis of all cohorts using the patients-treated population
  
  

• Adverse events [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  As a measure of safety
  
  
• Clinical laboratory tests [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  As a measure of safety
  
  
• Overall response rate [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Duration of response [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Profile of pharmacokinetics evaluations for JNJ-26481585 [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  Cmax, Area Under Curve, Tmax
  
  
• Profile of pharmacokinetics evaluations for VELCADE [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  Cmax, Area Under Curve, Tmax
  
  
• Bone cell morphology [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Pulse [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Heart rate [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Blood pressure [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Body temperature [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Height [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Weight [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  
• Body surface area [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  

This is an open-label (patient and study personnel will know what treatment is being administered), multicenter, dose escalation study. Increasing doses of JNJ-26481585 will be explored in combination with the standard VELCADE/dexamethasone dose. After the maximum tolerated dose (MTD) is determined, up to 24 patients will be entered in a treatment group to receive the MTD (and if deemed necessary a lower dose level) to further assess the safety and activity of this combination. There will be 3 phases in the study: a Screening Phase (from signing of informed consent until immediately before dosing), an open-label Treatment Phase (from the first dose of JNJ-26481585 and VELCADE-dexamethasone until the End of Treatment Visit), and a Posttreatment/Follow-up Phase. Patients who achieve a positive response to treatment at the end of Cycle 1 will continue to receive JNJ-26481585 and VELCADE-dexamethasone for a maximum of 11 cycles (eight 3-week treatment cycles, followed by three 5-week treatment cycles). Patients with progressive disease (PD) or unacceptable toxicity will be withdrawn from treatment. In the Follow-Up Phase, patients whose disease has not progressed or who discontinued treatment for reasons other than PD will be assessed approximately every 6 weeks until PD is recorded or until the start of subsequent therapy. The study will end when all patients have been assessed with PD, or 12 months after the last patient is enrolled, whichever is earlier. Patient safety will be monitored. Drug A, JNJ-26481585, will be taken orally on Days 1, 3, and 5 of each week at doses starting at 6 mg and escalating to 12 mg. Drug B, VELCADE, will be given by subcutaneous injection (under the skin) at a dose of 1.3 mg/m2 on Days 1, 4, 8, and 11 of each 21-day cycle (Cycles 1 to 8) and on Days 1, 8, 15, and 22 of each 35-day cycle (Cycles 9-11). Drug C, dexamethasone, will be taken orally on the day of and after VELCADE at a dose of 20 mg. Dosing may be adjusted, based on tolerability.