Trial Outcomes & Findings for Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma (NCT NCT01083602)

Last Updated: 2017-12-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

after eight cycyles of treatment (24 weeks)

Results posted on

2017-12-21

Participant Flow

Participant milestones

Participant milestones
Measure	Panobinostat + Bortezomib & Dexamethasone panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Study STARTED	55
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Panobinostat + Bortezomib & Dexamethasone panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Study Adverse Event	11
Overall Study New Cancer Therapy	2
Overall Study Death	1
Overall Study Withdrawal by Subject	5
Overall Study Lack of Efficacy	36

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Age, Continuous	61.9 years STANDARD_DEVIATION 10.54 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: after eight cycyles of treatment (24 weeks)

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Overall Response Rate (PR+nCR+CR)	34.5 percentage of participants Interval 22.2 to 46.7

SECONDARY outcome

Timeframe: after eight cycyles of treatment (24 weeks)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Responders to Treatment Complete Response (CR)	0 participants Interval 22.2 to 46.7
Responders to Treatment near Complete Response(nCR)	1 participants
Responders to Treatment Partial Response (PR)	18 participants
Responders to Treatment Minimal Response (MR)	10 participants
Responders to Treatment No Change	20 participants
Responders to Treatment Pregressive Disease (PD)	3 participants
Responders to Treatment Unknown	3 participants

SECONDARY outcome

Timeframe: after eight cycyles of treatment (24 weeks)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Time to Response (Greater Than or Equal to PR) Based on Investigator Assessment	51.8 Days Standard Deviation 30.92

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set (FAS)

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

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Progression-free Survival	164.0 days Interval 107.0 to 204.0

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS

Time from randomization until objective tumor progression; does not include deaths-- Kaplan-Meier estimates

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Time to Progression	164.0 Days Interval 107.0 to 204.0

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS

Kaplan Meier estimates- median time to event

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib & Dexamethasone n=55 Participants panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Over All Survival	559.0 Days Interval 329.0 to 682.0

Adverse Events

PAN + BTZ + Dex

Serious events: 39 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PAN + BTZ + Dex n=55 participants at risk PAN + BTZ + Dex
Blood and lymphatic system disorders Anaemia	7.3% 4/55
Blood and lymphatic system disorders Febrile neutropenia	1.8% 1/55
Blood and lymphatic system disorders Neutropenia	1.8% 1/55
Blood and lymphatic system disorders Pancytopenia	1.8% 1/55
Blood and lymphatic system disorders Thrombocytopenia	27.3% 15/55
Cardiac disorders Atrial fibrillation	1.8% 1/55
Gastrointestinal disorders Abdominal pain	1.8% 1/55
Gastrointestinal disorders Diarrhoea	5.5% 3/55
Gastrointestinal disorders Diverticulum	1.8% 1/55
Gastrointestinal disorders Gastritis	1.8% 1/55
Gastrointestinal disorders Haemorrhoids	1.8% 1/55
Gastrointestinal disorders Nausea	1.8% 1/55
Gastrointestinal disorders Oesophagitis	1.8% 1/55
Gastrointestinal disorders Pancreatitis	1.8% 1/55
General disorders Asthenia	3.6% 2/55
General disorders Pyrexia	9.1% 5/55
Hepatobiliary disorders Cholecystitis	1.8% 1/55
Hepatobiliary disorders Hepatic function abnormal	1.8% 1/55
Hepatobiliary disorders Hepatic ischaemia	1.8% 1/55
Infections and infestations Arthritis bacterial	1.8% 1/55
Infections and infestations Cellulitis	3.6% 2/55
Infections and infestations Clostridium difficile colitis	1.8% 1/55
Infections and infestations Clostridium difficile infection	1.8% 1/55
Infections and infestations Influenza	3.6% 2/55
Infections and infestations Parainfluenzae virus infection	1.8% 1/55
Infections and infestations Pneumonia	14.5% 8/55
Infections and infestations Postoperative wound infection	1.8% 1/55
Infections and infestations Sepsis	7.3% 4/55
Infections and infestations Septic shock	5.5% 3/55
Infections and infestations Sinusitis	1.8% 1/55
Infections and infestations Skin infection	1.8% 1/55
Infections and infestations Staphylococcal sepsis	1.8% 1/55
Infections and infestations Urinary tract infection	1.8% 1/55
Injury, poisoning and procedural complications Alcohol poisoning	1.8% 1/55
Investigations Neutrophil count decreased	1.8% 1/55
Investigations Platelet count decreased	1.8% 1/55
Investigations White blood cell count decreased	1.8% 1/55
Metabolism and nutrition disorders Dehydration	5.5% 3/55
Metabolism and nutrition disorders Hypercalcaemia	3.6% 2/55
Metabolism and nutrition disorders Hyperkalaemia	1.8% 1/55
Metabolism and nutrition disorders Hyponatraemia	1.8% 1/55
Metabolism and nutrition disorders Hypophagia	1.8% 1/55
Musculoskeletal and connective tissue disorders Back pain	5.5% 3/55
Musculoskeletal and connective tissue disorders Bone pain	1.8% 1/55
Nervous system disorders Lethargy	1.8% 1/55
Nervous system disorders Peroneal nerve palsy	1.8% 1/55
Psychiatric disorders Alcoholism	1.8% 1/55
Psychiatric disorders Confusional state	1.8% 1/55
Psychiatric disorders Depression	1.8% 1/55
Psychiatric disorders Mental status changes	1.8% 1/55
Renal and urinary disorders Renal failure acute	7.3% 4/55
Renal and urinary disorders Renal impairment	3.6% 2/55
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.6% 2/55
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.8% 1/55
Respiratory, thoracic and mediastinal disorders Hypoxia	1.8% 1/55
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.8% 1/55
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.8% 1/55
Vascular disorders Hypotension	5.5% 3/55
Vascular disorders Orthostatic hypotension	1.8% 1/55

Other adverse events

Other adverse events
Measure	PAN + BTZ + Dex n=55 participants at risk PAN + BTZ + Dex
Blood and lymphatic system disorders Anaemia	41.8% 23/55
Blood and lymphatic system disorders Neutropenia	20.0% 11/55
Blood and lymphatic system disorders Thrombocytopenia	41.8% 23/55
Eye disorders Lacrimation increased	9.1% 5/55
Eye disorders Vision blurred	18.2% 10/55
Gastrointestinal disorders Abdominal discomfort	9.1% 5/55
Gastrointestinal disorders Abdominal distension	20.0% 11/55
Gastrointestinal disorders Abdominal pain	14.5% 8/55
Gastrointestinal disorders Abdominal pain upper	12.7% 7/55
Gastrointestinal disorders Constipation	34.5% 19/55
Gastrointestinal disorders Diarrhoea	70.9% 39/55
Gastrointestinal disorders Dyspepsia	10.9% 6/55
Gastrointestinal disorders Flatulence	12.7% 7/55
Gastrointestinal disorders Nausea	60.0% 33/55
Gastrointestinal disorders Stomatitis	12.7% 7/55
Gastrointestinal disorders Vomiting	29.1% 16/55
General disorders Asthenia	18.2% 10/55
General disorders Chest pain	5.5% 3/55
General disorders Chills	7.3% 4/55
General disorders Fatigue	67.3% 37/55
General disorders Oedema	10.9% 6/55
General disorders Oedema peripheral	38.2% 21/55
General disorders Pyrexia	14.5% 8/55
Infections and infestations Candida infection	5.5% 3/55
Infections and infestations Oral candidiasis	5.5% 3/55
Infections and infestations Rhinitis	5.5% 3/55
Infections and infestations Sinusitis	5.5% 3/55
Infections and infestations Tooth infection	5.5% 3/55
Infections and infestations Upper respiratory tract infection	32.7% 18/55
Infections and infestations Urinary tract infection	7.3% 4/55
Injury, poisoning and procedural complications Contusion	10.9% 6/55
Injury, poisoning and procedural complications Fall	5.5% 3/55
Investigations Blood creatinine increased	10.9% 6/55
Investigations Weight decreased	14.5% 8/55
Metabolism and nutrition disorders Decreased appetite	41.8% 23/55
Metabolism and nutrition disorders Dehydration	10.9% 6/55
Metabolism and nutrition disorders Hyperglycaemia	9.1% 5/55
Metabolism and nutrition disorders Hypocalcaemia	5.5% 3/55
Metabolism and nutrition disorders Hypokalaemia	23.6% 13/55
Metabolism and nutrition disorders Hypomagnesaemia	12.7% 7/55
Metabolism and nutrition disorders Hyponatraemia	10.9% 6/55
Metabolism and nutrition disorders Hypophosphataemia	7.3% 4/55
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 4/55
Musculoskeletal and connective tissue disorders Back pain	16.4% 9/55
Musculoskeletal and connective tissue disorders Bone pain	7.3% 4/55
Musculoskeletal and connective tissue disorders Muscle spasms	9.1% 5/55
Musculoskeletal and connective tissue disorders Muscular weakness	16.4% 9/55
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.3% 4/55
Musculoskeletal and connective tissue disorders Myalgia	16.4% 9/55
Musculoskeletal and connective tissue disorders Pain in extremity	7.3% 4/55
Nervous system disorders Amnesia	5.5% 3/55
Nervous system disorders Dizziness	38.2% 21/55
Nervous system disorders Dysgeusia	23.6% 13/55
Nervous system disorders Headache	21.8% 12/55
Nervous system disorders Hypoaesthesia	10.9% 6/55
Nervous system disorders Neuropathy peripheral	27.3% 15/55
Nervous system disorders Paraesthesia	5.5% 3/55
Nervous system disorders Peripheral sensory neuropathy	5.5% 3/55
Nervous system disorders Syncope	9.1% 5/55
Nervous system disorders Tremor	7.3% 4/55
Psychiatric disorders Confusional state	7.3% 4/55
Psychiatric disorders Depression	5.5% 3/55
Psychiatric disorders Insomnia	23.6% 13/55
Respiratory, thoracic and mediastinal disorders Cough	16.4% 9/55
Respiratory, thoracic and mediastinal disorders Dyspnoea	34.5% 19/55
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	9.1% 5/55
Respiratory, thoracic and mediastinal disorders Epistaxis	10.9% 6/55
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.3% 4/55
Skin and subcutaneous tissue disorders Dry skin	5.5% 3/55
Skin and subcutaneous tissue disorders Ecchymosis	5.5% 3/55
Skin and subcutaneous tissue disorders Hyperhidrosis	5.5% 3/55
Skin and subcutaneous tissue disorders Pruritus	14.5% 8/55
Skin and subcutaneous tissue disorders Rash	7.3% 4/55
Skin and subcutaneous tissue disorders Skin lesion	5.5% 3/55
Vascular disorders Deep vein thrombosis	7.3% 4/55
Vascular disorders Haematoma	5.5% 3/55
Vascular disorders Hot flush	7.3% 4/55
Vascular disorders Hypertension	5.5% 3/55
Vascular disorders Hypotension	16.4% 9/55
Vascular disorders Orthostatic hypotension	7.3% 4/55

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER