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NCT00742027

Phase II Study of Oral Panobinostat in Adult Participants With Relapsed/Refractory Classical Hodgkin's Lymphoma

Completed Phase 2 Results posted Last updated 28 July 2021
What this trial tests

Phase 2 trial testing Panobinostat in Classical Hodgkin's Lymphoma in 129 participants. Completed in 12 August 2013.

Timeline
16 September 2008
Primary endpoint
12 August 2013
12 August 2013

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment129
Start date16 September 2008
Primary completion12 August 2013
Estimated completion12 August 2013
Sites46 locations across France, Italy, New Zealand, Malaysia, Belgium, United Kingdom, Germany, Israel

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Classical Hodgkin's Lymphoma. 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.

Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria Primary · From the start of the treatment of last participant up to 32 weeks

ORR was number of participants with best overall disease response of complete response(CR)/partial response(PR).Best overall disease response was best disease response recorded from start of treatment until disease progression/recurrence.CR=complete normalization of all index nodal,extranodal lesions,complete disappearance of all extranodal lesions.PR=50% decrease in SPD for up to 6 identified dominant lesions (splenic,hepatic nodules) from baseline.Stable=neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease (PD), reference smallest sum diameters while

Complete Response
GroupValue95% CI
Panobinostat5
Partial Response
GroupValue95% CI
Panobinostat30
Stable Disease
GroupValue95% CI
Panobinostat71
Progressive Disease
GroupValue95% CI
Panobinostat14
Unknown
GroupValue95% CI
Panobinostat9
Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) Secondary · From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years)

Best overall radiological response (CT/MRI) was recorded from start of treatment until progression/ recurrence. CR=complete normalization of all index nodal,extranodal lesions,complete disappearance of all extranodal lesions.PR=50% decrease in SPD for up to 6 identified dominant lesions (splenic,hepatic nodules) from baseline.Stable=neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease (PD), reference smallest sum diameters while on study.Progression=50% increase in sum of longest diameter of all target lesions,from smallest sum of longest diameter of a

Complete Response
GroupValue95% CI
Panobinostat0.8
Partial Response
GroupValue95% CI
Panobinostat20.9
Stable Disease
GroupValue95% CI
Panobinostat56.6
Progressive Disease
GroupValue95% CI
Panobinostat15.5
Unknown
GroupValue95% CI
Panobinostat6.2
Time To Overall Disease Response in Responders Secondary · From the start of treatment up to approximately 5 years

Time to overall disease response (CR or PR) was defined as the time from the date of randomization/start of treatment to the date of first documented disease response (PR or CR). Per Cheson response criteria, CR= is a complete normalization of all index nodal and extranodal lesions and complete disappearance of all extranodal lesions. PR= is a 50% decrease in the SPD for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. Participants were considered responders if they had a partial or complete response to a treatment while in the study as per Investigator

GroupValue95% CI
Panobinostat9.96.0 – 12.1
Duration of Overall Disease Response Secondary · From the start of treatment up to approximately 5 years

Duration of overall response (CR or PR) was defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to lymphoma. Per Cheson response criteria, CR= is a complete normalization of all index nodal and extranodal lesions and complete disappearance of all extranodal lesions. PR= is a 50% decrease in the SPD for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. Participants were considered responders if they had a partial or complete response to a treatment while in the study.

GroupValue95% CI
Panobinostat30.117.4 – 35.9
Progression Free Survival (PFS) Secondary · From the start of treatment up to approximately 5 years

Progression-free survival (PFS) was defined as the time from the date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a participant has not had an event, progression-free survival was censored at the date of the last adequate assessment.

GroupValue95% CI
Panobinostat6.15.4 – 8.3
The Overall Survival (OS) Secondary · Baseline to date of death from any cause (up to approximately 5 years)

OS was the duration from date of randomization to date of death from any cause. If a participant has not had an event, overall survival was censored at the date of the last adequate assessment.

GroupValue95% CI
Panobinostat34.90.7 – 53
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat Secondary · Up to approximately 5 years

An AE is the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) occurring after signing the informed consent even if the event is not considered to be related to the study drug(s). SAEs are AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

AEs
GroupValue95% CI
Panobinostat100
SAEs
GroupValue95% CI
Panobinostat39.5
Deaths
GroupValue95% CI
Panobinostat45.0
Maximum Observed Concentration (Cmax) of Panobinostat Secondary · Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
GroupValue95% CI
Panobinostat41.88± 22.165
The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat Secondary · Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
GroupValue95% CI
Panobinostat1.10.30 – 6.10
Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat Secondary · Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
GroupValue95% CI
Panobinostat233.38± 112.138
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) for Panobinostat Secondary · Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
GroupValue95% CI
Panobinostat239.36± 104.263

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 5 years. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Panobinostat
Serious: 51/129 (40%)
Deaths:

Serious adverse events (64 terms)

ReactionSystemPanobinostat
ThrombocytopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
HypotensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Device related infectionInfections and infestations
Lower respiratory tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
Deep vein thrombosisVascular disorders
Febrile neutropeniaBlood and lymphatic system disorders
Haemorrhagic disorderBlood and lymphatic system disorders
Idiopathic thrombocytopenic purpuraBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
Sinus tachycardiaCardiac disorders
Ventricular hypokinesiaCardiac disorders
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
GastritisGastrointestinal disorders
NauseaGastrointestinal disorders
Other adverse events (126 terms — click to expand)

ReactionSystemPanobinostat
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
DysgeusiaNervous system disorders
PruritusSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Upper respiratory tract infectionInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Oedema peripheralGeneral disorders
LeukopeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
AnxietyPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Dry mouthGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Dry skinSkin and subcutaneous tissue disorders
DyspepsiaGastrointestinal disorders
NasopharyngitisInfections and infestations
InsomniaPsychiatric disorders
PetechiaeSkin and subcutaneous tissue disorders
DepressionPsychiatric disorders
RashSkin and subcutaneous tissue disorders
Non-cardiac chest painGeneral disorders
Blood creatinine increasedInvestigations

Most-reported serious reactions: Thrombocytopenia, Anaemia, Pneumonia, Sepsis, Dyspnoea, Atrial fibrillation, Hypotension, Neutropenia.

Data from ClinicalTrials.gov NCT00742027 adverse events section.

Sponsor's own description

This study evaluated the efficacy of oral panobinostat in participants with refractory/relapsed classical Hodgkins lymphoma (HL) who have received prior treatment with high dose chemotherapy and autologous stem cell transplant. Safety of panobinostat also was assessed. Other markers that may correlate with efficacy or safety were explored.

Publications & conference data

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

  1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
    Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
  2. Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy.
    Singh AK, Bishayee A, Pandey AK. · · 2018 · cited 152× · PMID 29882797 · DOI 10.3390/nu10060731
  3. Targeting Histone Deacetylases in Diseases: Where Are We?
    Benedetti R, Conte M, Altucci L. · · 2015 · cited 91× · PMID 24382114 · DOI 10.1089/ars.2013.5776
  4. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
    Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
  5. Modulating epigenetic modifications for cancer therapy (Review).
    Castro-Muñoz LJ, Ulloa EV, Sahlgren C, Lizano M, et al · · 2023 · cited 62× · PMID 36799181 · DOI 10.3892/or.2023.8496
  6. Modulation of antigen-presenting cells by HDAC inhibitors: implications in autoimmunity and cancer.
    Woan KV, Sahakian E, Sotomayor EM, Seto E, et al · · 2012 · cited 54× · PMID 22105512 · DOI 10.1038/icb.2011.96
  7. Immune regulatory effects of panobinostat in patients with Hodgkin lymphoma through modulation of serum cytokine levels and T-cell PD1 expression.
    Oki Y, Buglio D, Zhang J, Ying Y, et al · · 2014 · cited 50× · PMID 25105535 · DOI 10.1038/bcj.2014.58
  8. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma.
    Chari A, Cho HJ, Dhadwal A, Morgan G, et al · · 2017 · cited 40× · PMID 29296798 · DOI 10.1182/bloodadvances.2017007427

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00742027.

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