Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Status: | Completed |
---|---|
Conditions: | Blood Cancer, Hematology |
Therapuetic Areas: | Hematology, Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 4/21/2016 |
Start Date: | December 2009 |
End Date: | July 2015 |
A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination 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.
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.
We found this trial at
41
sites
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Dayton CCOP We are a regional non-profit cancer research consortium serving the Miami Valley area...
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Miami Shores, Florida 33138
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3322 West End Avenue
Nashville, Tennessee 37203
Nashville, Tennessee 37203
(615)329-SCRI (7274)
Sarah Cannon Research Institute Sarah Cannon Research Institute (SCRI) is a global strategic research organization...
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New Orleans, Louisiana 70115
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Pittsburgh, Pennsylvania 15224
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