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Trial record 47 of 138 for:    lbh-589

Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00743288
Recruitment Status : Completed
First Posted : August 28, 2008
Results First Posted : April 25, 2014
Last Update Posted : May 8, 2014
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Oncotherapeutics

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Melphalan
Drug: Panobinostat
Enrollment 40

Recruitment Details This is a multicenter study
Pre-assignment Details  
Arm/Group Title Melphalan and Panobinostat Schedule A Melphalan and Panobinostat Schedule B1 Melphalan and Panobinostat Schedule B2 Melphalan and Panobinostat Schedule C Melphalan and Panobinostat Schedule D1 Melphalan and Panobinostat Schedule D2 Melphalan and Panobinostat Schedule D3
Hide Arm/Group Description 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1. 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1. 20 mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1. 15 mg/daily of LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle 15 mg/daily of LBH589 PO and melphalan PO at 0.10 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle 20 mg/daily of LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle
Period Title: Overall Study
Started 3 3 6 7 6 6 9 [1]
Completed 0 0 1 0 0 1 0
Not Completed 3 3 5 7 6 5 9
Reason Not Completed
Adverse Event             1             1             2             2             1             1             2
Withdrawal by Subject             0             0             1             0             0             1             1
Progressive disease (PD)             2             0             1             4             5             3             6
Worsening of condition (Not PD)             0             2             1             1             0             0             0
[1]
6 subjects were enrolled in phase 1 and 3 subjects were enrolled as part of the phase 2 expansion.
Arm/Group Title Melphalan and Panobinostat (LBH589)
Hide Arm/Group Description

Schedule A: 10mg/daily of LBH589 per orem (PO) on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.

Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1.

Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 40 participants
65.4
(34.2 to 88.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
15
  37.5%
Male
25
  62.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   5.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  10.0%
White
32
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
2
   5.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
Prior regimens  
Median (Full Range)
Unit of measure:  Number of prior regimens
Number Analyzed 40 participants
Number of prior regimens
4
(1 to 16)
Number of Bortezomib-containing prior regimens
2
(0 to 9)
1.Primary Outcome
Title Maximum Tolerated Dose (MTD)
Hide Description Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
MTD for Melphalan and Panobinostat was reached in the cohort of 6 participants who received 20 mg/daily LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1 of each cycle. Three additional patients were enrolled as part of the phase 2 expansion.
Arm/Group Title Melphalan and Panobinostat Schedule D3
Hide Arm/Group Description:
20mg daily LBH589 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: mg LBH589
20
2.Primary Outcome
Title MTD
Hide Description Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Melphalan and Panobinostat Schedule D3
Hide Arm/Group Description:
20mg daily LBH589 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: mg/kg melphalan
0.05
3.Primary Outcome
Title Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan
Hide Description Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.
Time Frame 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Melphalan and Panobinostat Schedule A Melphalan and Panobinostat Schedule B Melphalan and Panobinostat Schedule C Melphalan and Panobinostat Schedule D Melphalan and Panobinostat All Patients
Hide Arm/Group Description:
10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.

Schedules B1 and B2 B1: 10 mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 of a 28 day schedule and 0.04 mg/kg melphalan on days 1, 3 and 5 of week 1.

B2:20 mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 of a 28 day schedule and 0.04 mg/kg melphalan on days 1, 3 and 5 of week 1

0.05 mg/kg melphalan on days 1, 3 and 5 of week 1 and 20 mg of LBH589 on days 1, 3, and 5 of weeks 1 and 2.

Schedules D1, D2 and D3

D1:LBH589 15mg/daily and melphalan 0.05mg/kg on days 1, 3 and 5 of week 1 D2: LBH589 15mg and daily melphalan 0.10 mg/kg on days 1, 3 and 5 of week 1 D3: LBH589 20mg daily and melphalan 0.05mg/kg on days days 1, 3 and 5 of week 1

Data for all patients irrespective of dosage
Overall Number of Participants Analyzed 3 9 7 21 40
Measure Type: Number
Unit of Measure: participants
CR 0 0 0 0 0
VGPR 0 2 0 0 2
PR 0 1 0 0 1
MR 0 0 0 0 0
SD (stable disease) 1 5 5 12 23
Progressive disease (PD) 2 1 2 9 14
ORR (CR+VGPR+ PR) 0 3 0 0 3
CBR (ORR+MR) 0 3 0 0 3
4.Secondary Outcome
Title Duration of Response
Hide Description [Not Specified]
Time Frame First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only three patients had responses.
Arm/Group Title Melphalan and Panobinostat Schedule B
Hide Arm/Group Description:

B1: 10mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1.

B2: 20mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1.

Overall Number of Participants Analyzed 3
Median (Full Range)
Unit of Measure: months
8.1
(0 to 17.2)
5.Secondary Outcome
Title Time to Progression
Hide Description [Not Specified]
Time Frame Time from the start of treatment to progressive disease
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All cohorts were analyzed
Arm/Group Title Melphalan and Panobinostat
Hide Arm/Group Description:

Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.

Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1.

Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Overall Number of Participants Analyzed 40
Median (Full Range)
Unit of Measure: months
1.6
(0.6 to 2.7)
Time Frame 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Melphalan and Panobinostat
Hide Arm/Group Description

Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.

Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1.

Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

All-Cause Mortality
Melphalan and Panobinostat
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Melphalan and Panobinostat
Affected / at Risk (%) # Events
Total   7/40 (17.50%)    
Infections and infestations   
Sepsis * 1  1/40 (2.50%)  1
Gram-negative sepsis * 1  1/40 (2.50%)  1
Injury, poisoning and procedural complications   
Vertebral compression fracture * 1  1/40 (2.50%)  1
Metabolism and nutrition disorders   
Hypecalcemia  1  1/40 (2.50%)  1
Hyponatremia  1  1/40 (2.50%)  1
Psychiatric disorders   
Altered mental status * 1  1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonia * 1  1/40 (2.50%)  1
Vascular disorders   
Deep vein thrombosis with oulmonary embolism * 1  1/40 (2.50%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Melphalan and Panobinostat
Affected / at Risk (%) # Events
Total   22/40 (55.00%)    
Blood and lymphatic system disorders   
Anemia (>=grade 3)  1  6/40 (15.00%)  6
Leukopenia  1  6/40 (15.00%)  6
Lymphopenia  1  9/40 (22.50%)  9
Neutropenia  1  11/40 (27.50%)  11
Thrombocytopenia  1  10/40 (25.00%)  10
Metabolism and nutrition disorders   
Hyponatremia  1  2/40 (5.00%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE V4.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Director, Clinical Operations
Organization: Oncotherapeutics
Phone: 323-623-1200
Responsible Party: Oncotherapeutics
ClinicalTrials.gov Identifier: NCT00743288     History of Changes
Other Study ID Numbers: CDR0000612441
ONCOTHER-CLBH589BUS15T ( Other Identifier: Oncotherapeutics )
LBH ( Other Identifier: Oncotherapeutics )
First Submitted: August 27, 2008
First Posted: August 28, 2008
Results First Submitted: January 21, 2014
Results First Posted: April 25, 2014
Last Update Posted: May 8, 2014