Trial Outcomes & Findings for LBH589 in Refractory Myelodysplastic Syndromes (MDS) (NCT NCT00594230)
NCT ID: NCT00594230
Last Updated: 2021-11-22
Results Overview
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.
TERMINATED
PHASE2
26 participants
Every 8 weeks up to 24 months on-study.
2021-11-22
Participant Flow
Participant milestones
| Measure |
Panobinostat 30 mg
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
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 Study
STARTED
|
16
|
10
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
15
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
LBH589 in Refractory Myelodysplastic Syndromes (MDS)
Baseline characteristics by cohort
| Measure |
Panobinostat 30 mg
n=16 Participants
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
n=10 Participants
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
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
75 years
n=5 Participants
|
74 years
n=7 Participants
|
75 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
10 participants
n=7 Participants
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 8 weeks up to 24 months on-study.Population: 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
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.
Outcome measures
| Measure |
Panobinostat 30 mg
n=15 Participants
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
n=9 Participants
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 Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of diseasePopulation: Study terminated early, no results are available for this endpoint as the analysis was not done.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Every 8 weeks up to 24 months on-studyPopulation: Study terminated early, no results are available for this endpoint as the analysis was not done
Hematologic measures will include total WBC and platelets
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Every 8 weeks up to 24 months on-studyPopulation: Study terminated early, no results are available for this endpoint as the analysis was not done
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsPopulation: Study terminated early, no results are available for this endpoint as the analysis was not done
Time to treatment failure is defined as measuring the time between cycle 1 day 1 to discontinuation for any reason.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 months on-study, patients followed every 3 months in follow-upPopulation: Study terminated early, no results are available for this endpoint as the analysis was not done
The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsThe reported incidence of AEs and SAEs with an onset on or after the initiation of therapy was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Outcome measures
| Measure |
Panobinostat 30 mg
n=16 Participants
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
n=10 Participants
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.
|
|---|---|---|
|
Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS by Measuring the Number of Participants With Adverse Events
|
15 Participants
|
9 Participants
|
Adverse Events
Panobinostat 20 mg
Panobinostat 30 mg
Serious adverse events
| Measure |
Panobinostat 20 mg
n=10 participants at risk
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
n=16 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
20.0%
2/10
|
12.5%
2/16
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/10
|
25.0%
4/16
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
0.00%
0/10
|
6.2%
1/16
|
|
Investigations
Platelet count decreased
|
0.00%
0/10
|
6.2%
1/16
|
|
General disorders
Pain
|
0.00%
0/10
|
6.2%
1/16
|
|
General disorders
General disorders and administration site conditions - Other, compartment syndrome
|
0.00%
0/10
|
6.2%
1/16
|
|
Infections and infestations
Infections and infestations - Other, unspecified
|
0.00%
0/10
|
6.2%
1/16
|
|
Cardiac disorders
Atrial Fibrillation
|
10.0%
1/10
|
0.00%
0/16
|
|
Blood and lymphatic system disorders
Anemia
|
10.0%
1/10
|
0.00%
0/16
|
Other adverse events
| Measure |
Panobinostat 20 mg
n=10 participants at risk
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
n=16 participants at risk
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.
|
|---|---|---|
|
Investigations
Platelet Count Decreased
|
60.0%
6/10
|
93.8%
15/16
|
|
Blood and lymphatic system disorders
Anemia
|
70.0%
7/10
|
75.0%
12/16
|
|
General disorders
Fatigue
|
70.0%
7/10
|
75.0%
12/16
|
|
Investigations
Neutrophil Count Decreased
|
40.0%
4/10
|
93.8%
15/16
|
|
Gastrointestinal disorders
Diarrhea
|
80.0%
8/10
|
50.0%
8/16
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
2/10
|
75.0%
12/16
|
|
Gastrointestinal disorders
Nausea
|
60.0%
6/10
|
50.0%
8/16
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
60.0%
6/10
|
37.5%
6/16
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
80.0%
8/10
|
18.8%
3/16
|
|
Investigations
White Blood Cell Decreased
|
20.0%
2/10
|
50.0%
8/16
|
|
Nervous system disorders
Dizziness
|
50.0%
5/10
|
25.0%
4/16
|
|
General disorders
Edema
|
30.0%
3/10
|
31.2%
5/16
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness
|
30.0%
3/10
|
31.2%
5/16
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
20.0%
2/10
|
31.2%
5/16
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.0%
3/10
|
18.8%
3/16
|
|
General disorders
Fever
|
30.0%
3/10
|
18.8%
3/16
|
|
Gastrointestinal disorders
Vomiting
|
30.0%
3/10
|
18.8%
3/16
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
0.00%
0/10
|
31.2%
5/16
|
|
Gastrointestinal disorders
Constipation
|
10.0%
1/10
|
18.8%
3/16
|
|
Nervous system disorders
Dysgeusia
|
20.0%
2/10
|
12.5%
2/16
|
|
Gastrointestinal disorders
Gastrointestinal Disorders - Other, Stomatitis
|
10.0%
1/10
|
18.8%
3/16
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
20.0%
2/10
|
6.2%
1/16
|
|
General disorders
Non-Cardiac Chest Pain
|
20.0%
2/10
|
12.5%
2/16
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
2/10
|
12.5%
2/16
|
|
Gastrointestinal disorders
Abdominal Pain
|
20.0%
2/10
|
6.2%
1/16
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/10
|
18.8%
3/16
|
|
Cardiac disorders
Cardiac Disorders - Other, Systolic Murmur
|
10.0%
1/10
|
6.2%
1/16
|
|
Psychiatric disorders
Depression
|
10.0%
1/10
|
6.2%
1/16
|
|
Cardiac disorders
Electrocardiogram Qt Corrected Interval Prolonged
|
30.0%
3/10
|
0.00%
0/16
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
20.0%
2/10
|
6.2%
1/16
|
|
General disorders
General Disorders And Administration Site Conditions - Other, Pain At Port Site
|
30.0%
3/10
|
0.00%
0/16
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
10.0%
1/10
|
6.2%
1/16
|
|
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other, Ecchymosis
|
30.0%
3/10
|
0.00%
0/16
|
|
Cardiac disorders
Cardiac Disorders - Other, Tachycardia
|
20.0%
2/10
|
0.00%
0/16
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
2/10
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/10
|
6.2%
1/16
|
|
Nervous system disorders
Headache
|
20.0%
2/10
|
0.00%
0/16
|
|
Vascular disorders
Hematoma
|
20.0%
2/10
|
0.00%
0/16
|
|
Endocrine disorders
Hyperthyroidism
|
10.0%
1/10
|
6.2%
1/16
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/10
|
6.2%
1/16
|
|
Vascular disorders
Hypotension
|
20.0%
2/10
|
0.00%
0/16
|
|
Psychiatric disorders
Insomnia
|
10.0%
1/10
|
6.2%
1/16
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic And Mediastinal Disorders - Other, Hemoptysis
|
10.0%
1/10
|
6.2%
1/16
|
|
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other, Petechiae
|
10.0%
1/10
|
6.2%
1/16
|
|
Infections and infestations
Skin Infection
|
10.0%
1/10
|
6.2%
1/16
|
|
Infections and infestations
Upper Respiratory Infection
|
10.0%
1/10
|
6.2%
1/16
|
|
Renal and urinary disorders
Urinary Frequency
|
10.0%
1/10
|
6.2%
1/16
|
|
Investigations
Weight Loss
|
0.00%
0/10
|
6.2%
1/16
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER