ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 138 for:    lbh-589

LBH589 in Refractory Myelodysplastic Syndromes (MDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00594230
Recruitment Status : Terminated (Per protocol, the results of a planned interim analysis demonstrated insufficient efficacy and led to early termination of the study.)
First Posted : January 15, 2008
Results First Posted : December 19, 2012
Last Update Posted : November 13, 2015
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myelodysplastic Syndromes (MDS)
Intervention Drug: Panobinostat
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Panobinostat 30 mg Panobinostat 20 mg
Hide Arm/Group Description Panobinostat(30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator. Panobinostat(20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Period Title: Overall Study
Started 16 10
Completed 1 1
Not Completed 15 9
Arm/Group Title Panobinostat 30 mg Panobinostat 20 mg Total
Hide Arm/Group Description Panobinostat(30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator. Panobinostat(20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator. Total of all reporting groups
Overall Number of Baseline Participants 16 10 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants 10 participants 26 participants
75
(59 to 86)
74
(64 to 84)
75
(59 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 10 participants 26 participants
Female
1
   6.3%
6
  60.0%
7
  26.9%
Male
15
  93.8%
4
  40.0%
19
  73.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants 10 participants 26 participants
16 10 26
1.Primary Outcome
Title Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.
Hide Description Overall response rate (ORR) is defined by the modified International Working Group (IWG) Response Criteria for MDS. In the marrow, Complete Response (CR) is <= 5% blasts present with normal maturation of all cell lines. In peripheral blood, CR is defined as hemoglobin >= 11 g/dL, ANC >= 1000/mL, and platelets >= 100,000 with 0% blasts present. Partial Response (PR) is defined the same as CR with blasts decreased by >= 50% and >= 5% blasts in the marrow.
Time Frame Every 8 weeks up to 24 months on-study.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients assessed for response prior to early study termination - one patient in each arm was not evaluable due to coming off-study prior to assessment
Arm/Group Title Panobinostat 30 mg Panobinostat 20 mg
Hide Arm/Group Description:
Panobinostat(30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Panobinostat(20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Overall Number of Participants Analyzed 15 9
Measure Type: Number
Unit of Measure: participants
0 0
2.Secondary Outcome
Title Time to Disease Progression
Hide Description

Time to disease progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

NOTE: Study terminated early, no results are available for this endpoint

Time Frame Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Hematologic Improvement, Including Transfusion Independence
Hide Description

Hematologic measures will include total WBC and platelets

NOTE: Study terminated early, no results are available for this endpoint

Time Frame Every 8 weeks up to 24 months on-study
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Duration of Response
Hide Description

Duration of response is defined as the time from when objective response is realized until time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Objective Response = CR + PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

NOTE: Study terminated early, no results are available for this endpoint

Time Frame Every 8 weeks up to 24 months on-study
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Median Time to Treatment Failure
Hide Description

Time to treatment failure is defined as measuring the time between cycle 1 day 1 to discontinuation for any reason.

NOTE: Study terminated early, no results are available for this endpoint

Time Frame 24 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Median Overall Survival
Hide Description

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

NOTE: Study terminated early, no results are available for this endpoint

Time Frame 24 months on-study, patients followed every 3 months in follow-up
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS
Hide Description NOTE: Study terminated early, no results are available for this endpoint
Time Frame 24 months
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Panobinostat 20 mg Panobinostat 30 mg
Hide Arm/Group Description Panobinostat(20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator. Panobinostat(30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
All-Cause Mortality
Panobinostat 20 mg Panobinostat 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Panobinostat 20 mg Panobinostat 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   3/10 (30.00%)   6/16 (37.50%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  0/10 (0.00%)  4/16 (25.00%) 
Anemia  1  1/10 (10.00%)  0/16 (0.00%) 
Cardiac disorders     
Atrial Fibrillation  1  1/10 (10.00%)  0/16 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain  1  2/10 (20.00%)  2/16 (12.50%) 
General disorders     
Pain  1  0/10 (0.00%)  1/16 (6.25%) 
General disorders and administration site conditions - Other, compartment syndrome  1  0/10 (0.00%)  1/16 (6.25%) 
Infections and infestations     
Infections and infestations - Other, pneumonia  1  0/10 (0.00%)  1/16 (6.25%) 
Infections and infestations - Other, unspecified  1  0/10 (0.00%)  1/16 (6.25%) 
Investigations     
Platelet count decreased  1  0/10 (0.00%)  1/16 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Panobinostat 20 mg Panobinostat 30 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   9/10 (90.00%)   15/16 (93.75%) 
Blood and lymphatic system disorders     
Anemia  1  7/10 (70.00%)  12/16 (75.00%) 
Cardiac disorders     
Cardiac Disorders - Other, Systolic Murmur  1  1/10 (10.00%)  1/16 (6.25%) 
Electrocardiogram Qt Corrected Interval Prolonged  1  3/10 (30.00%)  0/16 (0.00%) 
Cardiac Disorders - Other, Tachycardia  1  2/10 (20.00%)  0/16 (0.00%) 
Endocrine disorders     
Hyperthyroidism  1  1/10 (10.00%)  1/16 (6.25%) 
Gastrointestinal disorders     
Diarrhea  1  8/10 (80.00%)  8/16 (50.00%) 
Nausea  1  6/10 (60.00%)  8/16 (50.00%) 
Vomiting  1  3/10 (30.00%)  3/16 (18.75%) 
Gastroesophageal Reflux Disease  1  0/10 (0.00%)  5/16 (31.25%) 
Constipation  1  1/10 (10.00%)  3/16 (18.75%) 
Gastrointestinal Disorders - Other, Stomatitis  1  1/10 (10.00%)  3/16 (18.75%) 
Abdominal Pain  1  2/10 (20.00%)  1/16 (6.25%) 
General disorders     
Fatigue  1  7/10 (70.00%)  12/16 (75.00%) 
Edema  1  3/10 (30.00%)  5/16 (31.25%) 
Fever  1  3/10 (30.00%)  3/16 (18.75%) 
Non-Cardiac Chest Pain  1  2/10 (20.00%)  2/16 (12.50%) 
General Disorders And Administration Site Conditions - Other, Pain At Port Site  1  3/10 (30.00%)  0/16 (0.00%) 
Infections and infestations     
Skin Infection  1  1/10 (10.00%)  1/16 (6.25%) 
Upper Respiratory Infection  1  1/10 (10.00%)  1/16 (6.25%) 
Injury, poisoning and procedural complications     
Bruising  1  0/10 (0.00%)  3/16 (18.75%) 
Investigations     
Platelet Count Decreased  1  6/10 (60.00%)  15/16 (93.75%) 
Neutrophil Count Decreased  1  4/10 (40.00%)  15/16 (93.75%) 
White Blood Cell Decreased  1  2/10 (20.00%)  8/16 (50.00%) 
Weight Loss  1  0/10 (0.00%)  1/16 (6.25%) 
Metabolism and nutrition disorders     
Anorexia  1  2/10 (20.00%)  12/16 (75.00%) 
Hypomagnesemia  1  1/10 (10.00%)  1/16 (6.25%) 
Dehydration  1  2/10 (20.00%)  0/16 (0.00%) 
Hypokalemia  1  0/10 (0.00%)  1/16 (6.25%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  8/10 (80.00%)  3/16 (18.75%) 
Generalized Muscle Weakness  1  3/10 (30.00%)  5/16 (31.25%) 
Nervous system disorders     
Dizziness  1  5/10 (50.00%)  4/16 (25.00%) 
Peripheral Sensory Neuropathy  1  2/10 (20.00%)  5/16 (31.25%) 
Dysgeusia  1  2/10 (20.00%)  2/16 (12.50%) 
Headache  1  2/10 (20.00%)  0/16 (0.00%) 
Psychiatric disorders     
Depression  1  1/10 (10.00%)  1/16 (6.25%) 
Insomnia  1  1/10 (10.00%)  1/16 (6.25%) 
Renal and urinary disorders     
Urinary Frequency  1  1/10 (10.00%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  6/10 (60.00%)  6/16 (37.50%) 
Cough  1  3/10 (30.00%)  3/16 (18.75%) 
Nasal Congestion  1  2/10 (20.00%)  1/16 (6.25%) 
Epistaxis  1  2/10 (20.00%)  1/16 (6.25%) 
Respiratory, Thoracic And Mediastinal Disorders - Other, Hemoptysis  1  1/10 (10.00%)  1/16 (6.25%) 
Skin and subcutaneous tissue disorders     
Rash  1  2/10 (20.00%)  2/16 (12.50%) 
Skin And Subcutaneous Tissue Disorders - Other, Ecchymosis  1  3/10 (30.00%)  0/16 (0.00%) 
Dry Skin  1  0/10 (0.00%)  1/16 (6.25%) 
Skin And Subcutaneous Tissue Disorders - Other, Petechiae  1  1/10 (10.00%)  1/16 (6.25%) 
Vascular disorders     
Hematoma  1  2/10 (20.00%)  0/16 (0.00%) 
Hypotension  1  2/10 (20.00%)  0/16 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Results of a planned interim analysis demonstrated that the regimen did not demonstrate sufficient evidence of efficacy necessary to justify further enrollment. Per protocol, the results of this analysis led to early termination of the study.
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 sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Results Point of Contact
Name/Title: John Hainsworth, MD
Organization: Sarah Cannon Research Institute
Phone: 1-877-691-7274
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00594230     History of Changes
Other Study ID Numbers: SCRI MDS 07
First Submitted: December 19, 2007
First Posted: January 15, 2008
Results First Submitted: August 22, 2012
Results First Posted: December 19, 2012
Last Update Posted: November 13, 2015