Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Bortezomib

Dexamethasone acetate

Panobinostat

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Panobinostat was administered 3x week ( 2 weeks on 1 week off)

Bortezomib was administered 2 x week ( 2weeks on 1 week off)

Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

Placebo was administered 3x week ( 2 weeks on 1 week off)

Placebo

Novartis Pharmaceuticals

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.

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

Best overall response based on mEBMT criteria per investigator assessment

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.

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.

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, scale 0 -28, , 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.

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.

PAN+BTZ

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..

PBO+BTZ

Panobinostat + Bortezomib

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.

Placebo + Bortezomib

Total

Age, Continuous

Sex: Female, Male

Caucasian

Asian

Black

Other

Race/Ethnicity, Customized

Study Director

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.

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.

Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone

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 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.

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 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.

Disease Symptom wk 12 change baseline (n=215,243)

Disease Symptom wk 24 change baseline (n=148,177)

Disease Symptom wk 48 change baseline (n=37,26)

Side effects of treatment wk 12 chge (n=213,242)

Side effects of treatment wk 24 chge (n=148,175)

Side effects of treatment wk 48 chge (n=37,26)

Future perspective wk 12 chge (n=214,242)

Future perspective wk 24 chge (n=148,176)

Future perspective wk 48 chge (n=37,26)

Body image wk 12 chge (n=213,240)

Body image wk 24 chge (n=147,175)

Body image wk 48 chge (n=37,26)

European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group

Global health wk 12 change baseline (n=216,239)

Global health wk 24 change baseline (n=150,176)

Global health wk 48 change baseline (n=38,26)

Physical functioning wk 12 chge (n=217,242)

Physical functioning wk 24 chge (n=151,177)

Physical functioning wk 48 chge (n=38,26)

Role functioning wk 12 chge (n=215,237)

Role functioning wk 24 chge (n=150,176)

Role functioning wk 48 chge (n=38,26)

Cognitive functioning wk 12 chge (n=216,240)

Cognitive functioning wk 24 chge (n=149,176)

Cognitive functioning wk 48 chge (n=38,26)

Social functioning wk 12 chge (n=216,240)

Social functioning wk 24 chge (n=148,171)

Social functioning wk 48 chge (n=37,26)

Fatigue wk 12 chge (n=217,241)

Fatigue wk 24 chge (n=151,176)

Fatigue wk 48 chge(n=38,26)

Dyspnea wk 12 chge (n=217,240)

Dyspnea wk 24 chge (n=151,177)

Dyspnea wk 48 chge (n=38,26)

Insomnia wk 12 chge (n=216,239)

Insomnia wk 24 chge (n=149,176)

Insomnia wk 48 chge (n=38,26)

Appetite loss wk 12 chge (n=217,239)

Appetite loss wk 24 chge (n=151,176)

Appetite loss wk 48 chge (n=38,26)

Constipation wk 12 chge (n=215,240)

Constipation wk 24 chge (n=151,177)

Constipation wk 48 chge (n=38,25)

Diarrhea wk 12 chge (n=217,241)

Diarrhea wk 24 chge (n=150,177)

Diarrhea wk 48 chge (n=38,26)

European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group

Neurotoxicity wk 12 change baseline (n=212,240)

Neurotoxicity wk 24 change baseline (n=148,174)

Neurotoxicity wk 48 change baseline (n=35,26)

Physical wellbeing wk 12 chge (n=215,240)

Physical wellbeingwk 24 chge (n=150,176)

Physical wellbeing wk 48 chge (n=38,26)

Trial Outcomes wk 12 chge (n=209,236)

Trial Outcomes wk 24 chge (n=148,173)

Trial Outcomes wk 48 chge (n=35,26)

FACT-G Total wk 12 chge (n=213,240)

FACT-G Totalwk 24 chge (n=147,175)

FACT-G Total wk 48 chge (n=37,26)

FACT/GOGNTX Total wk 12 chge (n=206,230)

FACT/GOGNTX Total wk 24 chge (n=146,172)

FACT/GOGNTX Total wk 48 chge (n=35,26)

Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group

Overall Study

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Subjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Given 3 times a week, every other week in 28-day cycles.

panobinostat

ruxolitinib

This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).

In 2011 the treatment goals for MF focused on symptom-orientated palliation and quality of life. Both ruxolitinib and panobinostat, as single agents, had shown significant improvement in both of those treatment goals and ruxolitinib had also shown greater reductions in splenomegaly compared to the standard of care at that time. To further the benefit seen with ruxolitinib in MF patients, panobinostat was added to the treatment regimen to act synergistically in the blockade of the dysregulated pathway driving this disease.

The study was conducted in 2 phases - an escalation phase and an expansion phase.

Escalation phase: the study utilised the Bayesian Logistic Regression Model (BLRM), incorporating escalation with overdose control (EWOC), which is a well established method for dose escalation in oncology trials. Following this process, successive cohorts of 3 newly enrolled patients received increasing doses of ruxolitinib and panobinostat until the maximum tolerated dose (MTD) or recommended phase II dose (RPIID) was determined. Once the MTD and/or RPIID were suspected in a minimum of 3 patients, additional patients were enrolled to the same cohort level to reach a minimum of 9 evaluable patients. The process also included safety, PK/PD assessments and estimates of efficacy based on measures of splenic reduction at each dose level.

Expansion: following the determination of the MTD and/or RPIID, a dose expansion phase was conducted at that dose to further define the safety and tolerability of the combination. At least 13, and no more than 23, additional patients were to be enrolled into the expansion phase.

Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis

A Phase 1b, Open-label, Multi-center, Single Arm, Dose Finding Study to Assess Safety and Pharmacokinetics of the Oral Combination of Panobinostat and Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera-myelofibrosis (PPV-MF) or Post-essential Thrombocythemia-myelofibrosis (PET-MF)

Area under the plasma concentration versus time curve

Tmax: The time of maximum observed concentration sampled during a dosing interval.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Participants with metastatic hormone refractory prostate cancer received 20 milligrams per meter square (mg/m\^2) of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.

This Phase II single dose study was designed to characterize the safety, tolerability, and efficacy of intravenous (i.v.) panobinostat as a single-agent treatment in participants with hormone refractory prostate cancer.

Only male participants are eligible as it is a prostate cancer study.

Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer

A Phase II, Open Label, Single Arm Study of i.v. Panobinostat (LBH589) in Patients With Metastatic Hormone Refractory Prostate Cancer

The PFS rate was defined as the percentage of participants that were alive without documented disease progression at the end of 24 weeks from first study treatment. Disease Progression as per response evaluation criteria in solid tumors (RECIST) criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 centimeter (cm) at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of greater than or equal to (\>=) 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

The tumor response rate was defined as a percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST criteria. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

Duration of SD was the time from date of start of treatment to the date of event, defined as the first documented disease progression or death due to underlying cancer. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of \>=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. If a participant had not had an event, duration of SD was to be censored at the date of last assessment.

The PSA response was defined as a 50% decrease in PSA from baseline maintained for \>= 4 weeks, and without clinical or radiographic evidence of disease progression during this time period. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of \>= 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

The PSA progression was defined as a 50% rise from nadir and a minimum rise of 2 nanogram per milligram (ng/mL). Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of \>=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

PFS was defined as the time from the date of start of treatment to the date of first documented disease progression or death due to any cause. If a participant had not had a disease progression and was alive, the participant was to be censored using the RECIST. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of \>=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. Kaplan-Meier method was to be used to estimate the median PFS.

The overall survival was defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was to be censored at the date of last contact. Kaplan-Meier method was to be used to estimate overall survival.

An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.

Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.

Male

Sex/Gender, Customized

Full Analysis set (FAS) population included all participants who received at least 1 dose of study drug.

FAS population included all participants who received at least 1 dose of study drug.

Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks

Percentage of Participants With Tumor Response Rate

We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.

Percentage of Participants With Duration of Stable Disease (SD) Per RECIST

FAS population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate at 24 Weeks

Percentage of Participants With PSA Progression Rate at 24 Weeks

Median Progression-free Survival (PFS)

Overall Survival

SAEs

Safety set population included all participants who were randomized and received at least 1 dose of study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma	NCT01023308	Multiple Myelom...	Panobinostat Bortezomib Dexamethasone Placebo	18 Years -	Novartis
Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis	NCT01433445	Idiopathic Myel... Post Essential ... Post Polycythem...	panobinostat ruxolitinib	18 Years -	Novartis
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma	NCT01023308	Multiple Myelom...	Panobinostat Bortezomib Dexamethasone Placebo	18 Years -	Novartis
Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer	NCT00667862	Prostate Cancer	Panobinostat	18 Years -	Novartis
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma	NCT01023308	Multiple Myelom...	Panobinostat Bortezomib Dexamethasone Placebo	18 Years -	Novartis

Spots Global Cancer Trial Database for daci

Every month we try and update this database with for daci cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for daci

Every month we try and update this database with for daci cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for daci cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.