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PANORAMA_3: Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma

Sponsor
SecuraBio (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02654990
Collaborator
(none)
249
Enrollment
80
Locations
3
Arms
96.2
Anticipated Duration (Months)
3.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of three different regimens of PAN (20 mg TIW, 20 mg BIW, and 10 mg TIW) in combination with s.c. BTZ and Dex and to provide exposure, safety and efficacy data to identify the optimal regimen of PAN in a randomized, 3-arm parallel design. This study will also assess the impact of administering s.c. BTZ (in combination with PAN and Dex) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in patients ≤ 75 years of age. Patients > 75 years of age will receive for the entire treatment period s.c. BTZ weekly (in combination with PAN and Dex) until disease progression.

Patients will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons.

Patients who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks.

All patients will be followed for survival until the last patient entering long-term follow-up has completed a 3 year survival follow-up or discontinued earlier.

Condition or Disease Intervention/Treatment Phase
  • Drug: panobinostat capsules
  • Drug: bortezomib injection
  • Drug: dexamethasone tablets
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
249 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Open-label Phase 2 Study Evaluating the Safety and Efficacy of Three Different Regimens of Oral Panobinostat in Combination With Subcutaneous Bortezomib and Oral Dexamethasone in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma Who Have Been Previously Exposed to Immunomodulatory Agents
Actual Study Start Date :
Apr 27, 2016
Actual Primary Completion Date :
Oct 18, 2019
Anticipated Study Completion Date :
May 2, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A - 20mg PAN TIW

20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone

Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Names:
  • PAN, LBH589

    • Drug: bortezomib injection
    1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
    Other Names:
  • BTZ

    • Drug: dexamethasone tablets
    pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
    Other Names:
  • Dex

    		•
    Experimental: Arm B - 20mg PAN BIW

    20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone

    Drug: panobinostat capsules
    20mg, 10mg or 15mg (for dose reductions only)
    Other Names:
  • PAN, LBH589

    • Drug: bortezomib injection
    1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
    Other Names:
  • BTZ

    • Drug: dexamethasone tablets
    pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
    Other Names:
  • Dex

    		•
    Experimental: Arm C - 10mg PAN TIW

    10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone

    Drug: panobinostat capsules
    20mg, 10mg or 15mg (for dose reductions only)
    Other Names:
  • PAN, LBH589

    • Drug: bortezomib injection
    1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
    Other Names:
  • BTZ

    • Drug: dexamethasone tablets
    pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
    Other Names:
  • Dex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall response rate (ORR) up to 8 cycles [up to 8 cycles per patient, approximately 30 months]

      assessed according to IMWG guidelines

    Secondary Outcome Measures

    1. ORR throughout study [approximately 70 months]

    2. individual immunophenotypic complete response (CR) rate [approximately 30 and 70 months]

    3. Progression-free survival [approximately 30 and 70 months]

    4. Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ) [approximately 30 months]

    5. Time to progression [approximately 30 and 70 months]

    6. Time to response [approximately 30 and 70 months]

    7. Duration of response (DOR) [approximately 30 and 70 months]

    8. European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared [approximately 30 and 70 months]

      EORTC QLQ-C30 on-treatment and in post treatment follow-up

    9. individual stringent CR rate [approximately 30 and 70 months]

    10. individual CR rate [approximately 30 and 70 months]

    11. overall survival [approximately 30 and 70 months]

    12. individual Very Good Partial Response rate [approximately 30 and 70 months]

    13. Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time [approximately 30 and 70 months]

      FACT/GOG-Ntx on-treatment

    14. Time to reach Cmax for PAN and BTZ [approximately 30 months]

    15. Minimum observed plasma concentration (Cmin) for PAN and BTZ [approximately 30 months]

    16. Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ [24 hours after every dose, approximately 30 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • multiple myeloma as per IMWG 2014 definition

    • requiring treatment for relapsed or relapsed/refractory disease

    • measurable disease based on central protein assessment

    • 1 to 4 prior lines of therapy

    • prior IMiD exposure

    • acceptable lab values prior to randomization

    Exclusion Criteria:

    • primary refractory myeloma

    • refractory to bortezomib

    • concomitant anti-cancer therapy (other then BTZ/Dex and bisphosphonates)

    • prior treatment with DAC inhibitors

    • clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)

    • unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)

    Other protocol-defined inclusion/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Fayetteville Arkansas United States 72703
    2 Novartis Investigative Site Los Angeles California United States 90017
    3 Novartis Investigative Site Fort Collins Colorado United States 80528
    4 Novartis Investigative Site Gainesville Florida United States 32608
    5 Novartis Investigative Site Atlanta Georgia United States 30322
    6 Novartis Investigative Site Louisville Kentucky United States 40202
    7 Novartis Investigative Site Boston Massachusetts United States 02215
    8 Novartis Investigative Site Lake Success New York United States 11042
    9 Novartis Investigative Site Morgantown West Virginia United States 26506
    10 Novartis Investigative Site Prahran Victoria Australia 3181
    11 Novartis Investigative Site Hasselt Belgium 3500
    12 Novartis Investigative Site Barretos Sao Paulo Brazil 14784 400
    13 Novartis Investigative Site Sao Paulo SP Brazil 04537 081
    14 Novartis Investigative Site Sao Paulo Brazil 05403-000
    15 Novartis Investigative Site Edmonton Alberta Canada T6G 1Z2
    16 Novartis Investigative Site Kitchener Ontario Canada N2G 1G3
    17 Novartis Investigative Site Ostrava Poruba Czech Republic Czechia 708 52
    18 Novartis Investigative Site Praha Czechia 12808
    19 Novartis Investigative Site Bayonne Bayonne Cedex France 64109
    20 Novartis Investigative Site Avignon cedex 9 France 84902
    21 Novartis Investigative Site Grenoble France 38043
    22 Novartis Investigative Site La Roche sur Yon Cedex France 85295
    23 Novartis Investigative Site Lille France 59037
    24 Novartis Investigative Site Metz France 57000
    25 Novartis Investigative Site Nantes Cedex 1 France 44093
    26 Novartis Investigative Site Paris France 75231
    27 Novartis Investigative Site Pessac France 33604
    28 Novartis Investigative Site Bad Saarow Germany 15526
    29 Novartis Investigative Site Bayreuth Germany 95445
    30 Novartis Investigative Site Darmstadt Germany 64287
    31 Novartis Investigative Site Dresden Germany 01307
    32 Novartis Investigative Site Halle Saale Germany 06120
    33 Novartis Investigative Site Hamburg Germany 22763
    34 Novartis Investigative Site Kiel Germany 24105
    35 Novartis Investigative Site Leipzig Germany 04103
    36 Novartis Investigative Site Athens Greece 115 27
    37 Novartis Investigative Site Athens Greece 115 28
    38 Novartis Investigative Site Patras Greece 265 00
    39 Novartis Investigative Site Debrecen HUN Hungary 4032
    40 Novartis Investigative Site Budapest Hungary 1097
    41 Novartis Investigative Site Kaposvar Hungary 7400
    42 Novartis Investigative Site Nyiregyhaza Hungary 4400
    43 Novartis Investigative Site Roma RM Italy 00161
    44 Novartis Investigative Site Rimini RN Italy 47900
    45 Novartis Investigative Site Hwasun-gun Jeollanam-do Korea, Republic of 58128
    46 Novartis Investigative Site Seoul Korea, Republic of 03080
    47 Novartis Investigative Site Beirut Lebanon 166830
    48 Novartis Investigative Site Beirut Lebanon
    49 Novartis Investigative Site Sidon Lebanon 652
    50 VUmc, Hematology, PK2 BR012 Amsterdam Netherlands 1081 HV
    51 Albert Schweitzer ziekenhuis, Hematology Dordrecht Netherlands 3318 AT
    52 Novartis Investigative Site Oslo Norway NO 0450
    53 Novartis Investigative Site Lublin Poland 20 090
    54 Novartis Investigative Site Torun Poland 87 100
    55 Novartis Investigative Site Warszawa Poland 02 106
    56 Novartis Investigative Site Warszawa Poland 02 776
    57 Novartis Investigative Site Wroclaw Poland 50 367
    58 Novartis Investigative Site Braga Portugal 4710243
    59 Novartis Investigative Site Porto Portugal 4200-072
    60 Novartis Investigative Site Saint Petersburg Russian Federation 191024
    61 Novartis Investigative Site Saratov Russian Federation 410012
    62 Novartis Investigative Site Malaga Andalucia Spain 29010
    63 Novartis Investigative Site Salamanca Castilla Y Leon Spain 37007
    64 Novartis Investigative Site Barcelona Catalunya Spain 08035
    65 Novartis Investigative Site Barcelona Catalunya Spain 08036
    66 Novartis Investigative Site L'Hospitalet De Llobregat Catalunya Spain 08907
    67 Novartis Investigative Site La Laguna Santa Cruz De Tenerife Spain 38320
    68 Novartis Investigative Site Madrid Spain 28006
    69 Novartis Investigative Site Madrid Spain 28040
    70 Novartis Investigative Site Madrid Spain 28041
    71 Novartis Investigative Site Zaragoza Spain 50009
    72 Novartis Investigative Site Lulea Sweden SE 971 80
    73 Novartis Investigative Site Lund Sweden SE-221 85
    74 Novartis Investigative Site Uppsala Sweden SE-751 85
    75 Novartis Investigative Site Mueang Nonthaburi Muang Thailand 40002
    76 Novartis Investigative Site Bangkok Thailand 10330
    77 Novartis Investigative Site Chiang Mai Thailand 50200
    78 Novartis Investigative Site Ankara Turkey 06100
    79 Novartis Investigative Site Istanbul Turkey 34899
    80 Novartis Investigative Site Izmir Turkey 35340

    Sponsors and Collaborators

    • SecuraBio

    Investigators

    • Study Director: SecuraBio, SecuraBio

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SecuraBio
    ClinicalTrials.gov Identifier:
    NCT02654990
    Other Study ID Numbers:
    • CLBH589D2222
    First Posted:
    Jan 13, 2016
    Last Update Posted:
    Mar 19, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by SecuraBio
    multiple myeloma
    relapsed or relapsed/refractory
    LBH589
    panobinostat
    bortezomib
    dexamethasone
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Bortezomib
    Panobinostat

    Study Results

    No Results Posted as of Mar 19, 2021