Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments panobinostat, bortezomib
Phase phase 3
Targets HDAC, proteasome, HIF-1a, VEGF
Sponsor Novartis Pharmaceuticals
Start date December 2009
End date March 2015
Trial size 768 participants
Trial identifier NCT01023308, 2009-015507-52, CLBH589D2308

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
panobinostat LBH589
bortezomib
(Placebo Comparator)
bortezomib

Primary Outcomes

Measure
To compare progression-free survival in patients treated with panobinostat in combination with bortezomib and dexamethasone vs. patients treated by placebo in combination with bortezomib and dexamethasone.
time frame: 30 months

Secondary Outcomes

Measure
To compare overall survival in patients treated with panobinostat in combination with bortezomib and dexamethasone vs. patients treated by placebo in combination with bortezomib and dexamethasone.
time frame: 30 months
To compare overall response rate of partial or better response in patients treated with panobinostat in combination with bortezomib and dexamethasone vs. patients treated by placebo in combination with bortezomib and dexamethasone.
time frame: 30 months
To compare time to response and duration of response patients treated with panobinostat in combination with bortezomib and dexamethasone vs. patients treated by placebo in combination with bortezomib and dexamethasone.
time frame: 30 months
To assess safety of the combination therapy.
time frame: 30 months
To evaluate health-related quality of life and symptoms of multiple myeloma
time frame: 30 months

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Trial information was received from ClinicalTrials.gov and was last updated in September 2014.
Information provided to ClinicalTrials.gov by Novartis.