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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01023308
First received: November 30, 2009
Last updated: September 21, 2015
Last verified: September 2015

November 30, 2009
September 21, 2015
December 2009
March 2013   (final data collection date for primary outcome measure)
  • Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [ Time Frame: 45 months ] [ Designated as safety issue: No ]
  • 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: 45 months ] [ Designated as safety issue: No ]
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 ]
Complete list of historical versions of study NCT01023308 on ClinicalTrials.gov Archive Site
  • Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [ Time Frame: 45 months ] [ Designated as safety issue: No ]

    Best overall response based on mEBMT criteria per investigator assessment:

    Stringent complete response (sCR): CR as defined below plus:

    Normal FLC ratio and Absence of clonal cells in bone marrow Complete response: Negative immunofixation on serum and urine and Disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow Very good partial reaponse:Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h Partial response: ≥50% reduction of serum M-protein ≥90% urine M-protein reduction or <200 mg/24 h ≥50% decrease in soft-tissue plasmacytomas Stable disease: Not meeting criteria for CR, VGPR, PR or progressive disease

  • Time to Response Per Investigator Assessment (mEBMT Criteria) 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: 45 months ] [ Designated as safety issue: No ]
  • Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [ Time Frame: 45 months ] [ Designated as safety issue: No ]
  • Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone. [ Time Frame: 45 months ] [ Designated as safety issue: No ]

    EBMT criteria to assess myeloma response:

    • Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of lytic bone lesions, plus other factors)
    • Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others
    • Minimal Response (MR)- 25-49% reduction in serum monoclonal paraprotein plus others
    • Stable Disease (SD)- not MR or progressive disease (PD)
    • Progressive Disease (PD)- reappearance of monoclonal paraprotein, lytic bone lesions, other
    • Not Evaluable (NE).
  • European Organization for Research and Treatment of Cancer Multiple Myeloma Module( EORTC QLQ-MY20) -Change From Baseline by Treatment Group [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
    Higher values in the disease symptoms and side effects of treatment scores indicate worsening. Higher scores in the future perspective and body image scores indicate improvement. LS Means and SEM are estimated from the repeated measures model. Following factors and covariates are included in the repeated measurement model: time, treatment, treatment by time interaction, number of prior lines of anti-MM therapy (1/ 2 and 3), prior use of BTZ (Yes/ No), baseline score.Disease Symptom is the sum of 20 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-MY20 have the same score range of 0 -100. Decrease in symptom scores from baseline indicate improvement in symptoms.
  • European Organization for Research and Treatment of Cancer Quality of Life Questionaire : EORTC QLQ-C30 - Summary Statistics by Treatment Group [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 measures functional dimensions (physical, role, emotional, cognitive, and social), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), six single-item symptom scales (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Disease Symptom is the sum of 30 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-C30 have the same score range of 0 -100. For global health status and other functional scales, an increase from baseline indicates improvement of QoL. Whereas for symptoms scales, fatigue, dyspnea, insomnia, appetite loss, constipation and diarrhea, decrease in scores from baseline indicate improvement in symptoms.
  • FACT/GOG-NTX-Change From Baseline by Treatment Group [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
    The FACT/GOG-NTX was developed from the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System and focuses on four general quality of life domains for physical well being, functional well-being, social/family well-being, and emotional well-being, and includes additional items to characterize treatment-related neurotoxicity. Higher subscales/total scores represent higher QOL. In the case of the neurotoxicity subscale, lower scores correspond to higher neurotoxicity. The recall period referenced in the questionnaire is the past 7 days.Ranges for FACT-G subscales are as follows:.PWB, SWB and FWB scale 0 -28, EWB scale 0-24, NtxS scale 0-44, FACT/GOG-Ntx trial outcome index scale is 0-100 and FACT-G scale is also scaled 0-100. An increase from baseline in these scores indicate improvement.
  • 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 ]
Not Provided
Not Provided
 
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Panobinostat
    Other Name: LBH589
  • Drug: Bortezomib
  • Experimental: Panobinostat + Bortezomib + Dexamethasone
    Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Interventions:
    • Drug: Panobinostat
    • Drug: Bortezomib
  • Placebo Comparator: Placebo + Bortezomib + Dexamethasone
    Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
    Intervention: Drug: Bortezomib

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
768
July 2015
March 2013   (final data collection date for primary outcome measure)

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.

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Czech Republic,   Denmark,   Egypt,   Finland,   France,   Germany,   Greece,   Hong Kong,   Israel,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Mexico,   Netherlands,   Norway,   Poland,   Russian Federation,   Singapore,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom
 
NCT01023308
CLBH589D2308, 2009-015507-52
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP