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NCT02654990 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2024-07-12

Note: The study data was transferred to zr pharma\& following the divestment of panobinostat to pharma\&. Prior to study completion under the sponsorship of Secura Bio, the study was initiated and conducted in part under the sponsorship of Novartis. The purpose of this study is to investigate the safety and efficacy of 3 different regimens of panobinostat (20 milligrams \[mg\] thrice a week \[TIW\], 20 mg twice a week \[BIW\], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants \> 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression. Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons. Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks. All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

ORR Throughout the Study

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outcome · POSTED

iCR Rate

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outcome · POSTED

sCR Rate

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outcome · POSTED

CR Rate

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outcome · POSTED

VGPR Rate

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Maximum Plasma Concentration (Cmax): Panobinostat

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outcome · POSTED

Cmax: Bortezomib

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outcome · POSTED

Time to Reach Cmax (Tmax): Panobinostat

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outcome · POSTED

Tmax: Bortezomib

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outcome · POSTED

Exposure Response: Cmax for Panobinostat

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outcome · POSTED

Change From Baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Core 30-item Questionnaire (QLQ-C30) Global Health Status (GHS) Score

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outcome · POSTED

Change From Baseline in the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group-Neurotoxicity (GOG-Ntx) Neurotoxicity Subscale Score

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Time to Response (TTR)

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outcome · POSTED

Duration of Response (DOR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * multiple myeloma per International Myeloma Working Group 2014 definition * requiring treatment for relapsed or relapsed/refractory disease * measurable disease based on central protein assessment * received 1 to 4 prior lines of therapy * prior immunomodulatory agent(s) exposure * acceptable lab values prior to randomization Exclusion Criteria: * primary refractory myeloma * refractory to bortezomib * concomitant anti-cancer therapy (other than bortezomib/dexamethasone and bisphosphonates) * prior treatment with pan-deacetylase inhibitors * clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization) * unresolved diarrhea ≥ Common Terminology Criteria for adverse events grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome and inflammatory bowel disease) Other protocol-defined inclusion/exclusion criteria may apply.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    20 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone
    intervention Names
    1. Drug: Panobinostat Capsules
    2. Drug: Bortezomib Injection
    3. Drug: Dexamethasone tablets
    label
    Arm A - 20 mg Panobinostat TIW
    type
    EXPERIMENTAL
  2. description
    20 mg panobinostat BIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone
    intervention Names
    1. Drug: Panobinostat Capsules
    2. Drug: Bortezomib Injection
    3. Drug: Dexamethasone tablets
    label
    Arm B - 20 mg Panobinostat BIW
    type
    EXPERIMENTAL
  3. description
    10 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone
    intervention Names
    1. Drug: Panobinostat Capsules
    2. Drug: Bortezomib Injection
    3. Drug: Dexamethasone tablets
    label
    Arm C - 10 mg Panobinostat TIW
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A - 20 mg Panobinostat TIW
    2. Arm B - 20 mg Panobinostat BIW
    3. Arm C - 10 mg Panobinostat TIW
    description
    20 mg, 10 mg or 15 mg (for dose reductions only)
    name
    Panobinostat Capsules
    other Names
    1. PAN
    2. LBH589
    3. Farydak
    type
    DRUG
  2. arm Group Labels
    1. Arm A - 20 mg Panobinostat TIW
    2. Arm B - 20 mg Panobinostat BIW
    3. Arm C - 10 mg Panobinostat TIW
    description
    1.3 mg/square meter subcutaneous administration. Cycle 1-4: 2 weeks on/1 week off, BIW for participants ≤ 75 years at time of screening; once a week for participants \> 75 years. Cycle 5+: once a week for all participants.
    name
    Bortezomib Injection
    other Names
    1. BTZ
    2. Velcade
    type
    DRUG
  3. arm Group Labels
    1. Arm A - 20 mg Panobinostat TIW
    2. Arm B - 20 mg Panobinostat BIW
    3. Arm C - 10 mg Panobinostat TIW
    description
    Pre and 24 hours after bortezomib administration. Participants ≤ 75 years at time of screening: 20 mg/dose participants; \> 75 years: 10 mg/dose.
    name
    Dexamethasone tablets
    other Names
    1. Dex
    2. Decadron
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
248
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    ORR is defined as the percentage of participants with a confirmed partial response (PR) or better (immunophenotypic complete response \[iCR\] or stringent complete response \[sCR\] or complete response \[CR\] or very good partial response \[VGPR\]) as their best overall response after completion of up to 8 cycles of assigned study regimen. Each cycle was 21 days long. Best overall response was the best post-baseline confirmed overall response observed in a given participant and was determined based on overall responses observed at all post-baseline response assessments, recorded from randomization until progressive disease (PD), death, start of new therapy, withdrawal of consent, or end of study, whatever came first. ORR was assessed blindly per independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria.
    measure
    Overall Response Rate (ORR)
    time Frame
    Up to 168 days
secondary Outcomes
  1. description
    ORR is defined as the percentage of participants with a confirmed PR or better (iCR or sCR or CR or VGPR) as their best overall response throughout the entire study. Best overall response was the best post-baseline confirmed overall response observed in a given participant and was determined based on overall responses observed at all post-baseline response assessments, recorded from randomization until PD, death, start of new therapy, withdrawal of consent or end of study, whatever came first. ORR was assessed blindly per IRC according to IMWG criteria.
    measure
    ORR Throughout the Study
    time Frame
    Up to 5.2 years
  2. description
    iCR, based on IMWG criteria per blinded IRC assessment, is defined as: negative immunofixation of serum and urine; disappearance of any soft tissue plasmacytoma(s), in the case of any presence of soft tissue plasmacytoma(s) at baseline; less than 5% plasma cells in bone marrow; normal free light chain (FLC) ratio; absence of clonal plasma cells in bone marrow analyzed by immunohistochemistry or 2- to 4-color flow cytometry; absence of phenotypically aberrant plasma cells (clonal) in bone marrow (BM) with a minimum of 1 million total BM cells analyzed by multiparametric flow cytometry (\>4 colors). Results reported as percentage of participants achieving iCR.
    measure
    iCR Rate
    time Frame
    Up to 5.2 years
  3. description
    sCR, based on IMWG criteria per blinded IRC assessment, is defined as: negative immunofixation of serum and urine; disappearance of any soft tissue plasmacytoma(s), in the case of any presence of soft tissue plasmacytoma(s) at baseline; less than 5% plasma cells in bone marrow; normal FLC ratio; absence of clonal plasma cells in bone marrow analyzed by immunohistochemistry or 2- to 4-color flow cytometry. Results reported as percentage of participants achieving sCR.
    measure
    sCR Rate
    time Frame
    Up to 5.2 years
  4. description
    CR, based on IMWG criteria per blinded IRC assessment, is defined as: negative immunofixation of serum and urine; disappearance of any soft tissue plasmacytoma(s), in the case of any presence of soft tissue plasmacytoma(s) at baseline; less than 5% plasma cells in bone marrow; in case the only measurable disease at baseline is the serum FLC assessment, a normal FLC ratio of 0.26 to 1.65 is required additionally to qualify for CR. Results reported as percentage of participants achieving CR.
    measure
    CR Rate
    time Frame
    Up to 5.2 years
  5. description
    VGPR, based on IMWG criteria per blinded IRC assessment, is defined as: serum and/or urine M protein detectable by immunofixation but not on protein electrophoresis, or ≥90% reduction from baseline in serum) and urine M protein \<100 milligrams/24 hours); in the case of the presence of any soft tissue plasmacytoma(s) at baseline, a reduction in the sum of the products of the cross-diameters by ≥50% from baseline is required; in case the only measurable disease in a participant at baseline is the serum FLC level (that is, no measurable disease in serum and urine PEP), a decrease of \>90% in the difference between involved and uninvolved FLC levels from baseline is required. Results reported as percentage of participants achieving VGPR.
    measure
    VGPR Rate
    time Frame
    Up to 5.2 years
  6. description
    PFS, assessed based on IMWG criteria per blind IRC assessment, is defined as the time from date of randomization to date of first documented disease progression or death (regardless of cause of death).
    measure
    Progression-free Survival (PFS)
    time Frame
    Up to 5.2 years
  7. description
    OS is defined as the time from date of randomization to the date of death due to any cause.
    measure
    Overall Survival (OS)
    time Frame
    Up to 5.2 years
  8. description
    Serial blood samples were collected for panobinostat Cmax analysis. Results are reported in nanograms/milliliter (ng/mL).
    measure
    Maximum Plasma Concentration (Cmax): Panobinostat
    time Frame
    Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
  9. description
    Serial blood samples were collected for bortezomib Cmax analysis. Results are reported in ng/mL.
    measure
    Cmax: Bortezomib
    time Frame
    Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
  10. description
    Serial blood samples were collected for panobinostat Tmax analysis. Results are reported in hours.
    measure
    Time to Reach Cmax (Tmax): Panobinostat
    time Frame
    Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
  11. description
    Serial blood samples were collected for bortezomib Tmax analysis. Results are reported in hours.
    measure
    Tmax: Bortezomib
    time Frame
    Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
  12. description
    The exposure-response relationship was assessed utilizing Cmax (Cycle 1 Day 1) for panobinostat versus the outcomes of ORR, grade 3/4 thrombocytopenia, and grade 3/4 diarrhea. Two statistical models were used: logistic regression models, in which these 3 outcomes were treated in a binary fashion according to their occurrence; Cox regression models, with the relevant outcomes being the time to occurrence of grade 3/4 thrombocytopenia and the time to occurrence of grade 3/4 diarrhea. Results are reported as model-based probability. An increase in the model-based probability indicates an increase in the occurrence of the outcomes (ORR, grade 3/4 thrombocytopenia, 3/4 diarrhea) with increasing values of Cmax (that is, with increasing dose of panobinostat).
    measure
    Exposure Response: Cmax for Panobinostat
    time Frame
    Up to 5.2 Years
Full study description
brief Summary
Note: The study data was transferred to zr pharma\& following the divestment of panobinostat to pharma\&. Prior to study completion under the sponsorship of Secura Bio, the study was initiated and conducted in part under the sponsorship of Novartis. The purpose of this study is to investigate the safety and efficacy of 3 different regimens of panobinostat (20 milligrams \[mg\] thrice a week \[TIW\], 20 mg twice a week \[BIW\], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants \> 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression. Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons. Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks. All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.
Source references
references
  1. citation
    Laubach JP, Schjesvold F, Mariz M, Dimopoulos MA, Lech-Maranda E, Spicka I, Hungria VTM, Shelekhova T, Abdo A, Jacobasch L, Polprasert C, Hajek R, Illes A, Wrobel T, Sureda A, Beksac M, Goncalves IZ, Blade J, Rajkumar SV, Chari A, Lonial S, Spencer A, Maison-Blanche P, Moreau P, San-Miguel JF, Richardson PG. Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study. Lancet Oncol. 2021 Jan;22(1):142-154. doi: 10.1016/S1470-2045(20)30680-X. Epub 2020 Dec 7.
    pmid
    33301738
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice