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Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma (MACS1271)

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ClinicalTrials.gov Identifier: NCT01083602
Recruitment Status : Completed
First Posted : March 10, 2010
Results First Posted : March 27, 2015
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Relapsed and Bortezomib Refractory Multiple Myeloma
Refractory Multiple Myeloma
Multiple Myeloma in Relapse
Interventions Drug: panobinostat
Drug: bortezomib
Drug: dexamethasone
Enrollment 55
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Period Title: Overall Study
Started 55
Completed 0
Not Completed 55
Reason Not Completed
Adverse Event             11
New Cancer Therapy             2
Death             1
Withdrawal by Subject             5
Lack of Efficacy             36
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Baseline Participants 55
Hide Baseline Analysis Population Description
The study population consisted of adult patients with relapsed and bortezomib-refractory MM who had received at least 2 prior lines of therapy and had been exposed to an IMiD (thalidomide or lenalidomide). Bortezomib-refractory was defined as demonstrated disease progression on or within 60 days of the last bortezomib -containing line of therapy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants
61.9  (10.54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Female
26
  47.3%
Male
29
  52.7%
1.Primary Outcome
Title Overall Response Rate (PR+nCR+CR)
Hide Description Overall response rate=(PR+nCR+CR) CR= < 5% plasma cells in bone marrow. No confirmation on bone marrow plasma cell (additional assessment) is needed to document CR except patients with non-secretory myeloma where the bone marrow examination must be repeated after an interval of at least 6 weeks, Absence of M-protein in serum and urine by immunofixation,nCR same as CR without out Absence of M-protein in serum and urine by immunofixation,PR+ 50% reduction of serum M-protein and sofft tissue Plasmacytomas all for more than 6 weeks.
Time Frame after eight cycyles of treatment (24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.5
(22.2 to 46.7)
2.Secondary Outcome
Title Responders to Treatment
Hide Description The primary endpoint for this phase II study of patients with bortezomib-refractory MM is response after a maximum of 8 cycles of therapy as defined by the modified EBMT criteria.
Time Frame after eight cycyles of treatment (24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0
near Complete Response(nCR) 1
Partial Response (PR) 18
Minimal Response (MR) 10
No Change 20
Pregressive Disease (PD) 3
Unknown 3
3.Secondary Outcome
Title Time to Response (Greater Than or Equal to PR) Based on Investigator Assessment
Hide Description Time to response is defined as the time from the date of first administration of study treatment to the date of first documented evidence of CR or nCR or PR (whichever status is recorded first). Patients who do not have a response of PR or better by the data cut-off date are censored.
Time Frame after eight cycyles of treatment (24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Mean (Standard Deviation)
Unit of Measure: Days
51.8  (30.92)
4.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) was defined as the time from the date of first study treatment to first occurrence of documented progressive disease /relapse or death. Time from randomization until disease progression or death by Kaplan-Meier estimates
Time Frame 24 weeks
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Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: days
164.0
(107.0 to 204.0)
5.Secondary Outcome
Title Time to Progression
Hide Description Time from randomization until objective tumor progression; does not include deaths-- Kaplan-Meier estimates
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: Days
164.0
(107.0 to 204.0)
6.Secondary Outcome
Title Over All Survival
Hide Description Kaplan Meier estimates- median time to event
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Panobinostat + Bortezomib & Dexamethasone
Hide Arm/Group Description:
panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: Days
559.0
(329.0 to 682.0)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PAN + BTZ + Dex
Hide Arm/Group Description PAN + BTZ + Dex
All-Cause Mortality
PAN + BTZ + Dex
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
PAN + BTZ + Dex
Affected / at Risk (%)
Total   39/55 (70.91%) 
Blood and lymphatic system disorders   
Anaemia  1  4/55 (7.27%) 
Febrile neutropenia  1  1/55 (1.82%) 
Neutropenia  1  1/55 (1.82%) 
Pancytopenia  1  1/55 (1.82%) 
Thrombocytopenia  1  15/55 (27.27%) 
Cardiac disorders   
Atrial fibrillation  1  1/55 (1.82%) 
Gastrointestinal disorders   
Abdominal pain  1  1/55 (1.82%) 
Diarrhoea  1  3/55 (5.45%) 
Diverticulum  1  1/55 (1.82%) 
Gastritis  1  1/55 (1.82%) 
Haemorrhoids  1  1/55 (1.82%) 
Nausea  1  1/55 (1.82%) 
Oesophagitis  1  1/55 (1.82%) 
Pancreatitis  1  1/55 (1.82%) 
General disorders   
Asthenia  1  2/55 (3.64%) 
Pyrexia  1  5/55 (9.09%) 
Hepatobiliary disorders   
Cholecystitis  1  1/55 (1.82%) 
Hepatic function abnormal  1  1/55 (1.82%) 
Hepatic ischaemia  1  1/55 (1.82%) 
Infections and infestations   
Arthritis bacterial  1  1/55 (1.82%) 
Cellulitis  1  2/55 (3.64%) 
Clostridium difficile colitis  1  1/55 (1.82%) 
Clostridium difficile infection  1  1/55 (1.82%) 
Influenza  1  2/55 (3.64%) 
Parainfluenzae virus infection  1  1/55 (1.82%) 
Pneumonia  1  8/55 (14.55%) 
Postoperative wound infection  1  1/55 (1.82%) 
Sepsis  1  4/55 (7.27%) 
Septic shock  1  3/55 (5.45%) 
Sinusitis  1  1/55 (1.82%) 
Skin infection  1  1/55 (1.82%) 
Staphylococcal sepsis  1  1/55 (1.82%) 
Urinary tract infection  1  1/55 (1.82%) 
Injury, poisoning and procedural complications   
Alcohol poisoning  1  1/55 (1.82%) 
Investigations   
Neutrophil count decreased  1  1/55 (1.82%) 
Platelet count decreased  1  1/55 (1.82%) 
White blood cell count decreased  1  1/55 (1.82%) 
Metabolism and nutrition disorders   
Dehydration  1  3/55 (5.45%) 
Hypercalcaemia  1  2/55 (3.64%) 
Hyperkalaemia  1  1/55 (1.82%) 
Hyponatraemia  1  1/55 (1.82%) 
Hypophagia  1  1/55 (1.82%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  3/55 (5.45%) 
Bone pain  1  1/55 (1.82%) 
Nervous system disorders   
Lethargy  1  1/55 (1.82%) 
Peroneal nerve palsy  1  1/55 (1.82%) 
Psychiatric disorders   
Alcoholism  1  1/55 (1.82%) 
Confusional state  1  1/55 (1.82%) 
Depression  1  1/55 (1.82%) 
Mental status changes  1  1/55 (1.82%) 
Renal and urinary disorders   
Renal failure acute  1  4/55 (7.27%) 
Renal impairment  1  2/55 (3.64%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  2/55 (3.64%) 
Dyspnoea exertional  1  1/55 (1.82%) 
Hypoxia  1  1/55 (1.82%) 
Pneumonitis  1  1/55 (1.82%) 
Pulmonary embolism  1  1/55 (1.82%) 
Vascular disorders   
Hypotension  1  3/55 (5.45%) 
Orthostatic hypotension  1  1/55 (1.82%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PAN + BTZ + Dex
Affected / at Risk (%)
Total   53/55 (96.36%) 
Blood and lymphatic system disorders   
Anaemia  1  23/55 (41.82%) 
Neutropenia  1  11/55 (20.00%) 
Thrombocytopenia  1  23/55 (41.82%) 
Eye disorders   
Lacrimation increased  1  5/55 (9.09%) 
Vision blurred  1  10/55 (18.18%) 
Gastrointestinal disorders   
Abdominal discomfort  1  5/55 (9.09%) 
Abdominal distension  1  11/55 (20.00%) 
Abdominal pain  1  8/55 (14.55%) 
Abdominal pain upper  1  7/55 (12.73%) 
Constipation  1  19/55 (34.55%) 
Diarrhoea  1  39/55 (70.91%) 
Dyspepsia  1  6/55 (10.91%) 
Flatulence  1  7/55 (12.73%) 
Nausea  1  33/55 (60.00%) 
Stomatitis  1  7/55 (12.73%) 
Vomiting  1  16/55 (29.09%) 
General disorders   
Asthenia  1  10/55 (18.18%) 
Chest pain  1  3/55 (5.45%) 
Chills  1  4/55 (7.27%) 
Fatigue  1  37/55 (67.27%) 
Oedema  1  6/55 (10.91%) 
Oedema peripheral  1  21/55 (38.18%) 
Pyrexia  1  8/55 (14.55%) 
Infections and infestations   
Candida infection  1  3/55 (5.45%) 
Oral candidiasis  1  3/55 (5.45%) 
Rhinitis  1  3/55 (5.45%) 
Sinusitis  1  3/55 (5.45%) 
Tooth infection  1  3/55 (5.45%) 
Upper respiratory tract infection  1  18/55 (32.73%) 
Urinary tract infection  1  4/55 (7.27%) 
Injury, poisoning and procedural complications   
Contusion  1  6/55 (10.91%) 
Fall  1  3/55 (5.45%) 
Investigations   
Blood creatinine increased  1  6/55 (10.91%) 
Weight decreased  1  8/55 (14.55%) 
Metabolism and nutrition disorders   
Decreased appetite  1  23/55 (41.82%) 
Dehydration  1  6/55 (10.91%) 
Hyperglycaemia  1  5/55 (9.09%) 
Hypocalcaemia  1  3/55 (5.45%) 
Hypokalaemia  1  13/55 (23.64%) 
Hypomagnesaemia  1  7/55 (12.73%) 
Hyponatraemia  1  6/55 (10.91%) 
Hypophosphataemia  1  4/55 (7.27%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  4/55 (7.27%) 
Back pain  1  9/55 (16.36%) 
Bone pain  1  4/55 (7.27%) 
Muscle spasms  1  5/55 (9.09%) 
Muscular weakness  1  9/55 (16.36%) 
Musculoskeletal pain  1  4/55 (7.27%) 
Myalgia  1  9/55 (16.36%) 
Pain in extremity  1  4/55 (7.27%) 
Nervous system disorders   
Amnesia  1  3/55 (5.45%) 
Dizziness  1  21/55 (38.18%) 
Dysgeusia  1  13/55 (23.64%) 
Headache  1  12/55 (21.82%) 
Hypoaesthesia  1  6/55 (10.91%) 
Neuropathy peripheral  1  15/55 (27.27%) 
Paraesthesia  1  3/55 (5.45%) 
Peripheral sensory neuropathy  1  3/55 (5.45%) 
Syncope  1  5/55 (9.09%) 
Tremor  1  4/55 (7.27%) 
Psychiatric disorders   
Confusional state  1  4/55 (7.27%) 
Depression  1  3/55 (5.45%) 
Insomnia  1  13/55 (23.64%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/55 (16.36%) 
Dyspnoea  1  19/55 (34.55%) 
Dyspnoea exertional  1  5/55 (9.09%) 
Epistaxis  1  6/55 (10.91%) 
Oropharyngeal pain  1  4/55 (7.27%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  3/55 (5.45%) 
Ecchymosis  1  3/55 (5.45%) 
Hyperhidrosis  1  3/55 (5.45%) 
Pruritus  1  8/55 (14.55%) 
Rash  1  4/55 (7.27%) 
Skin lesion  1  3/55 (5.45%) 
Vascular disorders   
Deep vein thrombosis  1  4/55 (7.27%) 
Haematoma  1  3/55 (5.45%) 
Hot flush  1  4/55 (7.27%) 
Hypertension  1  3/55 (5.45%) 
Hypotension  1  9/55 (16.36%) 
Orthostatic hypotension  1  4/55 (7.27%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01083602    
Other Study ID Numbers: CLBH589DUS71
First Submitted: March 8, 2010
First Posted: March 10, 2010
Results First Submitted: February 23, 2015
Results First Posted: March 27, 2015
Last Update Posted: December 21, 2017