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NCT00445068

Efficacy and Safety of LBH589B in Adult Patients With Multiple Myeloma

Terminated Phase 2 Results posted Last updated 14 July 2021
What this trial tests

Phase 2 trial testing LBH589 in Multiple Myeloma in 38 participants. Terminated before completion.

Timeline
16 April 2007
Primary endpoint
19 May 2008
25 December 2009

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment38
Start date16 April 2007
Primary completion19 May 2008
Estimated completion25 December 2009
Sites29 locations across United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety and Tolerability Secondary · From Start of the Study up to 57 Weeks approximately.

Adverse Event (AE) are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazard

Participants with Adverse Events
GroupValue95% CI
Panobinostat38
Deaths
GroupValue95% CI
Panobinostat7
On treatment deaths
GroupValue95% CI
Panobinostat3
Serious Adverse Events
GroupValue95% CI
Panobinostat17
Study-drug-related Serious Adverse Events
GroupValue95% CI
Panobinostat3
Adverse Events Leading to discontinuation
GroupValue95% CI
Panobinostat8
Time to Peak Concentration (Tmax) of Panobinostat Secondary · Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's pharmacokinetic (PK) profile, then Tmax will be missing for that subject. Tmax will be reported in units of h.

Day 1
GroupValue95% CI
Panobinostat1.70.2 – 5.2
Day 8
GroupValue95% CI
Panobinostat1.20.2 – 23.7
Maximum Plasma Concentration (Cmax) of Panobinostat Secondary · Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL.

Day 1
GroupValue95% CI
Panobinostat7.6± 5.52
Day 8
GroupValue95% CI
Panobinostat9.7± 6.51
Area Under the Plasma Concentration (AUC0-24) of Panobinostat Secondary · Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Area under the curve (AUC) is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours.

Day 1
GroupValue95% CI
Panobinostat72.0± 36.10
Day 8
GroupValue95% CI
Panobinostat81.6± 37.56
Last Observed Plasma Concentration (Clast) of Panobinostat Secondary · Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast.

Day 1
GroupValue95% CI
Panobinostat0.3± 0.18
Day 8
GroupValue95% CI
Panobinostat1.1± 1.13
Time of Clast (Tlast) of Panobinostat Secondary · Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h.

Day 1
GroupValue95% CI
Panobinostat47.824 – 50.2
Day 8
GroupValue95% CI
Panobinostat24.33.3 – 28.0

Adverse events — posted to ClinicalTrials.gov

Time frame: From Start of the Study up to 57 Weeks approximately.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Panobinostat
Serious: 17/38 (45%)
Deaths: 7/38

Serious adverse events (37 terms)

ReactionSystemPanobinostat
PneumoniaInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
DehydrationMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
DysphagiaGastrointestinal disorders
RetchingGastrointestinal disorders
General physical health deteriorationGeneral disorders
PainGeneral disorders
GastroenteritisInfections and infestations
InfectionInfections and infestations
Respiratory tract infectionInfections and infestations
Sepsis syndromeInfections and infestations
Streptococcal infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
Femoral neck fractureInjury, poisoning and procedural complications
Hip fractureInjury, poisoning and procedural complications
Multiple fracturesInjury, poisoning and procedural complications
Blood creatinine increasedInvestigations
Monoclonal immunoglobulin presentInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Other adverse events (52 terms — click to expand)

ReactionSystemPanobinostat
NauseaGastrointestinal disorders
FatigueGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Blood creatinine increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Weight decreasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
SomnolenceNervous system disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
HypoaesthesiaNervous system disorders
DepressionPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Productive coughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
Gait disturbanceGeneral disorders
PainGeneral disorders
Gastrointestinal infectionInfections and infestations
InfluenzaInfections and infestations
PneumoniaInfections and infestations

Most-reported serious reactions: Pneumonia, Hypercalcaemia, Thrombocytopenia, Diarrhoea, Nausea, Vomiting, Pyrexia, Dehydration.

Data from ClinicalTrials.gov NCT00445068 adverse events section.

Sponsor's own description

This study will evaluate the efficacy and safety of LBH589B in adult patients with multiple myeloma who have received at least two prior therapies and are refractory to their last therapy. Patients must have received in prior therapy either bortezomib or lenalidomide

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives.
    Pu J, Liu T, Wang X, Sharma A, et al · · 2024 · cited 36× · PMID 38654286 · DOI 10.1186/s40164-024-00507-5
  2. Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma.
    Dupéré-Richer D, Licht JD. · · 2017 · cited 32× · PMID 28441149 · DOI 10.1097/moh.0000000000000358
  3. Epimutational profile of hematologic malignancies as attractive target for new epigenetic therapies.
    Fratta E, Montico B, Rizzo A, Colizzi F, et al · · 2016 · cited 17× · PMID 27329599 · DOI 10.18632/oncotarget.10033
  4. Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications.
    Schütt J, Nägler T, Schenk T, Brioli A. · · 2021 · cited 8× · PMID 34439223 · DOI 10.3390/cancers13164069
  5. Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor.
    Redic KA, Hough SM, Price EM. · · 2016 · cited 8× · PMID 27274274 · DOI 10.2147/ott.s87962

Verify or expand the search:

Other trials of LBH589

Trials testing the same drug.

Other recruiting trials for Multiple Myeloma

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing