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
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety and tolerability and to establish the
      maximum tolerated dose of JNJ-26481585 combined with VELCADE and dexamethasone.
    

Detailed description: 
      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      toxicity will be withdrawn from treatment.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.
    

Intervention name(s): JNJ-2641585 / VELCADE / Dexamethasone
Intervention type(s): Drug
Intervention description(s): JNJ-26481585: type=range, unit=mg, number=6 to 12, form=capsules, route=oral use, on Days 1, 3, and 5 of each week. VELCADE: type=exact, unit=mg/m2, number=1.3, form=powder for solution for injection, route=subcutaneous use, 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). Dexamethasone: type=exact, unit=mg, number=20, form=tablets, route=oral use, on the day of and after VELCADE.
Intervention MeSH terms: Dexamethasone; Bortezomib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple myeloma that has relapsed or is progressive following prior therapy; Relapsed Multiple Myeloma; JNJ 26481585; VELCADE; Bortezomib; Dexamethasone