Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of
 HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded
 protein aggregates and triggers myeloma cell death. Combination of pan-DAC and protease
 inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated
 synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore,
 clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat
 and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and
 manageable toxicity profile.

 Given the medical need for improved treatment strategies for patients with previously treated
 and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind,
 placebo-controlled, parallel group Phase III study is to compare the results in
 progression-free survival of 2 combination therapies, panobinostat with bortezomib and
 dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously
 treated MM whose disease has recurred or progressed.
Inclusion Criteria:

 1. Patient has a previous diagnosis of multiple myeloma.

 2. Patient requires retreatment for multiple myeloma

 3. Patient has measurable M component in serum or urine at study screening

 Exclusion Criteria:

 1. Patient who has progressed under all prior lines of anti MM therapy

 2. Patient who has been treated by bortezomib before, and did not reach at least a minor
 response under this therapy, or progressed under it or within 60 days of last dose

 3. Patient has shown intolerance to bortezomib or to dexamethasone or components of these
 drugs or has any contraindication to one or the other drug , following locally
 applicable prescribing information

 4. Patient received prior treatment with DAC inhibitors including panobinostat

 5. Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG

 6. Patient taking medications with relative risk of prolonging the QT interval or
 inducing Torsade de pointes

 7. Female patient who is pregnant or breast feeding or with childbearing potential and
 not willing to use a double method of contraception up to 3 months after the end of
 study treatment. Male patient who is not willing to use a barrier method of
 contraception up to 3 months after the end of study treatment.

 Other protocol-defined inclusion/exclusion criteria may apply.