Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Panobinostat; Bortezomib; Dexamethasone; Placebo
Intervention description: Panobinostat was administered 3x week ( 2 weeks on 1 week off); Bortezomib was administered 2 x week ( 2weeks on 1 week off); Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration; Placebo was administered 3x week ( 2 weeks on 1 week off)
Intervention MeSH terms: Dexamethasone; Bortezomib; Panobinostat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 767.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloma; DACi; Bortezomib; Combination; Panobinostat; LBH589D; relapsed; Velcade®; Combination,

Summary:

      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.
    

Eligibility criteria:

        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.