Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01023308
First received: November 30, 2009
Last updated: July 7, 2014
Last verified: July 2014
  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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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: 768
Study Start Date: December 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (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
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01023308

  Show 213 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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: July 7, 2014
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 July 23, 2014