Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Patient has a previous diagnosis of multiple myeloma.
Patient requires retreatment for multiple myeloma
Patient has measurable M component in serum or urine at study screening

Criterios de exclusión

Patient who has progressed under all prior lines of anti MM therapy
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
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
Patient received prior treatment with DAC inhibitors including panobinostat
Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG
Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes
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.

Intervenciones

drug

Panobinostat

Panobinostat was administered 3x week ( 2 weeks on 1 week off)

drug

Bortezomib

Bortezomib was administered 2 x week ( 2weeks on 1 week off)

drug

Dexamethasone

Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

drug

Placebo

Placebo was administered 3x week ( 2 weeks on 1 week off)

A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Panobinostat

Bortezomib

Dexamethasone

Placebo

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores