A study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma

INTERVENTION: Product Name: panobinostat Product Code: LBH589 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Panobinostat CAS Number: 404950‐80‐7 Current Sponsor code: LBH589 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: panobinostat Product Code: LBH589 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Panobinostat CAS Number: 404950‐80‐7 Current Sponsor code: LBH589 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Velcade Product Name: Velcade Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: Bortezomib CAS Number: 179324‐69‐7 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1‐ Trade Name: Fortecortin Product Name: Fortecortin Pharmaceutical Form: Tablet INN or Proposed INN: Dexamethasone CAS Number: 50‐02‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ Trade Name: Fortecortin Product Name: Fortecortin Pharmaceutical Form: Tablet INN or Proposed INN: Dexamethasone CAS Number: 50‐02‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Trade Name: Fortecortin Product Name: Fortecortin Pharmaceutical Form: Tablet INN or Proposed INN: Dexamethasone CAS Number: 50‐02‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Trade Name: Fortecortin Product Name: Fortecortin Pharmaceutical Form: Tablet INN or Proposed INN: Dexamethasone CAS Number: 50‐02‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 8‐ Product Name: panobinostat Product Code: LBH589 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Panobinostat CAS Number: 404950‐80‐7 Cu CONDITION: Multiple Myeloma (MM), relapsed or relapsed‐and‐refractory ; MedDRA version: 16.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Secondary end point(s): 1. OS ; 2. ORR (comprising CR, nCR, and PR) ; 3. nCR +Cr ; 4. MRR ; 5. TTR ; 6. DOR ; 7. TTP ; 8. HRQoL and multiple myeloma symptoms as measured by: EORTC QLQ‐C30, EORTC QLQ‐MY20, and FACT/GOG‐NTX Timepoint(s) of evaluation of this end point: 1. to 7.: every 3 weeks during treatment and then every 6 weeks after end of treatment ; 8.: at screening, day 1 of each cycle and study evaluation completion INCLUSION CRITERIA: 1.Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions. All three of the following criteria must have been met: a.Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine b.Bone marrow (clonal) plasma cells = 10% or biopsy proven plasmacytoma c.Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections) 2.Patient with 1 to 3 prior lines of therapy who require retreatment of myeloma (cf IMWG 2003 ) for one of the 2 conditions below: b.Relapsed‐and‐refractory to a therapy, provided t PRIMARY OUTCOME: Main Objective: To compare progression‐free survival (PFS), in patients treated with PAN in combination with BTZ/Dex vs. patients treated with placebo in combination with BTZ/Dex Primary end point(s): PFS i.e. PD for patients not in CR or relapse for patients in CR (per investigator assessment based on modified EBMT criteria) or death from any cause Secondary Objective: Key Secondary; •To compare OS (overall survival); Other Secondary; •To compare ORR (overall response rate) comprising CR, nCR and PR; •To compare nCR plus CR rate (near complete response plus + complete response); •To compare MRR (minor response rate) ; •To compare TTR (time to response); •To compare TTP (time to progression); •To assess duration of response (DOR; from first occurring PR or better); •To assess safety of the combination therapy; •To assess health‐related quality of life and symptoms of multiple myeloma Timepoint(s) of evaluation of this end point: Every 3 weeks during treatment and then every 6 weeks after end of treatment a.Relapsed, defined by disease that recurred in a patient that responded under a prior therapy, by reaching a MR or better, and had not progressed under this therapy nor up to 60 days of last dose of this therapy. Patients priorly treated by BTZ may be eligible.