Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma |
Drug: Panobinostat Drug: Bortezomib |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| 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 |
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To assess safety of the combination therapy. [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
- To evaluate health-related quality of life and symptoms of multiple myeloma [ Time Frame: 30 months ] [ Designated as safety issue: No ]
| Enrollment: | 769 |
| Study Start Date: | December 2009 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Panobinostat + Bortezomib + Dexamethasone |
Drug: Panobinostat
Other Name: LBH589
Drug: Bortezomib
|
| Placebo Comparator: Placebo + Bortezomib + Dexamethasone | Drug: Bortezomib |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Hide Study Locations| United States, Arizona | |
| Arizona Oncology Associates Tucson (Carondelet & Wilmot) | |
| Phoenix, Arizona, United States | |
| United States, California | |
| Rau, Subramanyam | |
| Anaheim, California, United States, 92801 | |
| Bay Area Cancer Research | |
| Concord, California, United States, 94520 | |
| Southern California Permanente Medical Group SC | |
| Los Angeles, California, United States, 90027 | |
| Kaiser Permanente | |
| San Diego, California, United States, 92120 | |
| Kaiser Permanente - California Southern Kaiser Permanente SCPMG | |
| San Diego, California, United States | |
| Stanford University Medical Center School of Medicine | |
| Stanford, California, United States, 94304 | |
| United States, Florida | |
| Boca Raton Community Hospital SC | |
| Boca Raton, Florida, United States, 33486 | |
| Medical Specialist of Palm Beaches | |
| Lake Worth, Florida, United States, 33467 | |
| Innovative Medical Research of South Florida Dept.ofInnovativeMedResearch | |
| Miami Shores, Florida, United States, 33138 | |
| United States, Georgia | |
| Northeast Georgia Cancer Care | |
| Athens, Georgia, United States, 30607 | |
| Emory University School of Medicine/Winship Cancer Institute | |
| Atlanta, Georgia, United States, 30322 | |
| NorthWest Georgia Oncology Centers NW Georgia Oncology Centers PC | |
| Marietta, Georgia, United States, 30060 | |
| United States, Illinois | |
| Loyola University Chicago | |
| Marywood, Illinois, United States, 60153 | |
| Quincy Medical Group | |
| Quincy, Illinois, United States, 62301 | |
| United States, Louisiana | |
| LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center | |
| New Orleans, Louisiana, United States, 70115 | |
| United States, Maryland | |
| St. Agnes Hospital Healthcare Cancer Center | |
| Baltimore, Maryland, United States, 21229 | |
| Associates in Oncology/Hematology, P.C. | |
| Rockville, Maryland, United States, 20850 | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute | |
| Boston, Massachusetts, United States, 02115 | |
| United States, Michigan | |
| Newland Medical Associates, PC Newland Medical - Southfield | |
| Southfield, Michigan, United States | |
| United States, Minnesota | |
| Hubert H. Humphrey Cancer Center - Coon Rapids | |
| Edina, Minnesota, United States, 55435 | |
| Minnesota Oncology Hematology, P.A. Minnesota Oncology Hematology, | |
| Minneapolis, Minnesota, United States, 55404 | |
| United States, Missouri | |
| Missouri Cancer Associates Dept.ofMissouriCancerAssoc. | |
| Columbia, Missouri, United States, 65201 | |
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| East Orange VA Medical Center SC | |
| East Orange, New Jersey, United States, 07018-1095 | |
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| Mount Kisco Medical Group | |
| Mt. Kisco, New York, United States, 10549 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, North Dakota | |
| Legacy Pharma Research | |
| Bismarck, North Dakota, United States, 58501 | |
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| Dayton CCOP | |
| Dayton, Ohio, United States, 45429 | |
| Signal Point Hematology Oncology, Inc. | |
| Middletown, Ohio, United States, 45042 | |
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| Western Pennsylvania Cancer Institute /Western Penn Hospital Western Pann. Cancer Inst. | |
| Pittsburgh, Pennsylvania, United States, 15224 | |
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| Pharma Resource | |
| East Providence, Rhode Island, United States, 02915 | |
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| Vanderbilt Univeristy SC | |
| Nashville, Tennessee, United States, 37232 | |
| Sarah Cannon Research Institute | |
| Nashville, Tennessee, United States, 37203 | |
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| Cancer Center of the High Plains | |
| Amarillo, Texas, United States, 79106 | |
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| Houston, Texas, United States, 77030 | |
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| Columbia Basin Hematology SC | |
| Kennewick, Washington, United States, 99336 | |
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| Seattle, Washington, United States, 98104 | |
| St. Mary Medical Center | |
| Walla Walla, Washington, United States, 33962 | |
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| West Virginia University/ Mary Babb Randolph Cancer Center | |
| Morgantown, West Virginia, United States, 26506 | |
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| Würzburg, Germany, 97080 | |
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| Thessaloniki, Greece, GR 570 10 | |
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| Turkey | |
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| Adana, Turkey, 01330 | |
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| Ankara, Turkey, 06100 | |
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| Istanbul, Turkey, 34303 | |
| United Kingdom | |
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| Aberdeen, Scotland, United Kingdom, AB25 2ZN | |
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| Glasgow, United Kingdom, G12 0YN | |
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| London, United Kingdom, EC1A 7BE | |
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| London, United Kingdom, SE5 9RS | |
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| London, United Kingdom, W12 0HS | |
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| London, United Kingdom, WC1E 6HX | |
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| Manchester, United Kingdom, M20 4BX | |
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| Wolverhampton, United Kingdom, WV10 0QP | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01023308 History of Changes |
| Other Study ID Numbers: | CLBH589D2308, 2009-015507-52 |
| Study First Received: | November 30, 2009 |
| Last Updated: | April 19, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Novartis:
|
Myeloma DACi Bortezomib Combination, |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone acetate |
Dexamethasone Dexamethasone 21-phosphate Bortezomib BB 1101 Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Gastrointestinal Agents Glucocorticoids Hormones |
ClinicalTrials.gov processed this record on May 22, 2013