LBH589 in Refractory Myelodysplastic Syndromes (MDS)

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00594230
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 26
• Locations: 7
• Arms: 2
• Duration (Months): 37.9
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This will be a single arm Phase II study.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes (MDS)	Drug: Panobinostat	Phase 2

Detailed Description

LBH589 (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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of LBH589 in Refractory Myelodysplastic Syndromes (MDS) Patients
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat 20 mg Treatment with LBH589 (Panobinostat) 20 mg	Drug: Panobinostat; Panobinostat(20 mg or 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.; Other Names: LBH589
Experimental: Panobinostat 30 mg Treatment with LBH589 (Panobinostat) 30 mg	Drug: Panobinostat; Panobinostat(20 mg or 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.; Other Names: LBH589

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS. [Every 8 weeks up to 24 months on-study.]

   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.

Secondary Outcome Measures

1. Time to Disease Progression [Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease]

   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.

2. Hematologic Improvement, Including Transfusion Independence [Every 8 weeks up to 24 months on-study]

   Hematologic measures will include total WBC and platelets

3. Duration of Response [Every 8 weeks up to 24 months on-study]

   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.

4. Median Time to Treatment Failure [24 months]

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

5. Median Overall Survival [24 months on-study, patients followed every 3 months in follow-up]

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

6. Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS by Measuring the Number of Participants With Adverse Events [24 months]

   The 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).

• Male or female patients aged >= 18 years old.

• MDS patients who have failed hypomethylating (azacitidine or decitabine) therapy.

• Patients with 5q-cytogenic abnormalities must also have progressed on or been intolerant to lenalidomide.

• Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.

• CMML with >= 5% blasts will be eligible to enroll.

• ECOG PS 0, 1 or 2.

• Laboratory values must be as follows:

Bilirubin <= 1.5 mg/dL AST/SGOT <= 2.5 x ULN ALT/SGPT Creatinine <= 2.0 mg/dL or 24-hour Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN) Phosphorous >= LLN Calcium >= LLN Magnesium >= LLN

• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.

• Life expectancy >= 12 weeks.

Exclusion Criteria:

• Prior treatment with an HDAC inhibitor.

• Prior intensive chemotherapy or high dose ara-C (>= 1 gm/m2)

• More than one prior single agent chemotherapy regimen. Prior hydroxyurea for cytoreduction will be permitted however.

• Impaired cardiac function

• Active CNS disease, including leptomeningeal metastases.

• Unresolved diarrhea > CTCAE grade 1.

• Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.

• Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.

• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method.

• Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.

• Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).

• Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Patients with uncontrolled coagulopathy.

• Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
3	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
4	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
5	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
6	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
7	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Novartis Pharmaceuticals

Investigators

• Study Chair: Ian W. Flinn, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00594230
• Other Study ID Numbers: SCRI MDS 07
• First Posted: Jan 15, 2008
• Last Update Posted: Nov 22, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by SCRI Development Innovations, LLC: Myelodysplastic Syndromes (MDS); Refractory; LBH589
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Panobinostat

Study Results

Participant Flow

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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

Baseline Characteristics

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg	Total
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 Participants	16	10	26
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	75	74	75
Sex: Female, Male (Count of Participants)
Female	1 6.3%	6 60%	7 26.9%
Male	15 93.8%	4 40%	19 73.1%
Region of Enrollment (participants) [Number]
United States	16 100%	10 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.
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.

Outcome Measure Data

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
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.
Measure Participants	15	9
Number [participants]	0 0%	0 0%

2. Secondary Outcome

Title	Time to Disease Progression
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.
Time Frame	Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease

Outcome Measure Data

Analysis Population Description

Study terminated early, no results are available for this endpoint as the analysis was not done.

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	0	0

3. Secondary Outcome

Title	Hematologic Improvement, Including Transfusion Independence
Description	Hematologic measures will include total WBC and platelets
Time Frame	Every 8 weeks up to 24 months on-study

Outcome Measure Data

Analysis Population Description

Study terminated early, no results are available for this endpoint as the analysis was not done

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	0	0

4. Secondary Outcome

Title	Duration of Response
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.
Time Frame	Every 8 weeks up to 24 months on-study

Outcome Measure Data

Analysis Population Description

Study terminated early, no results are available for this endpoint as the analysis was not done

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	0	0

5. Secondary Outcome

Title	Median Time to Treatment Failure
Description	Time to treatment failure is defined as measuring the time between cycle 1 day 1 to discontinuation for any reason.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Study terminated early, no results are available for this endpoint as the analysis was not done

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	0	0

6. Secondary Outcome

Title	Median Overall Survival
Description	The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time Frame	24 months on-study, patients followed every 3 months in follow-up

Outcome Measure Data

Analysis Population Description

Study terminated early, no results are available for this endpoint as the analysis was not done

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	0	0

7. Secondary Outcome

Title	Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS by Measuring the Number of Participants With Adverse Events
Description	The 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
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat 30 mg	Panobinostat 20 mg
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.
Measure Participants	16	10
Count of Participants [Participants]	15 93.8%	9 90%

Adverse Events

Arm/Group Title	Panobinostat 20 mg		Panobinostat 30 mg
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Panobinostat 20 mg		Panobinostat 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		6/16 (37.5%)
Blood and lymphatic system disorders
Febrile neutropenia	0/10 (0%)		4/16 (25%)
Anemia	1/10 (10%)		0/16 (0%)
Cardiac disorders
Atrial Fibrillation	1/10 (10%)		0/16 (0%)
Gastrointestinal disorders
Abdominal Pain	2/10 (20%)		2/16 (12.5%)
General disorders
Pain	0/10 (0%)		1/16 (6.3%)
General disorders and administration site conditions - Other, compartment syndrome	0/10 (0%)		1/16 (6.3%)
Infections and infestations
Infections and infestations - Other, pneumonia	0/10 (0%)		1/16 (6.3%)
Infections and infestations - Other, unspecified	0/10 (0%)		1/16 (6.3%)
Investigations
Platelet count decreased	0/10 (0%)		1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Panobinostat 20 mg		Panobinostat 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/10 (90%)		15/16 (93.8%)
Blood and lymphatic system disorders
Anemia	7/10 (70%)		12/16 (75%)
Cardiac disorders
Cardiac Disorders - Other, Systolic Murmur	1/10 (10%)		1/16 (6.3%)
Electrocardiogram Qt Corrected Interval Prolonged	3/10 (30%)		0/16 (0%)
Cardiac Disorders - Other, Tachycardia	2/10 (20%)		0/16 (0%)
Endocrine disorders
Hyperthyroidism	1/10 (10%)		1/16 (6.3%)
Gastrointestinal disorders
Diarrhea	8/10 (80%)		8/16 (50%)
Nausea	6/10 (60%)		8/16 (50%)
Vomiting	3/10 (30%)		3/16 (18.8%)
Gastroesophageal Reflux Disease	0/10 (0%)		5/16 (31.3%)
Constipation	1/10 (10%)		3/16 (18.8%)
Gastrointestinal Disorders - Other, Stomatitis	1/10 (10%)		3/16 (18.8%)
Abdominal Pain	2/10 (20%)		1/16 (6.3%)
General disorders
Fatigue	7/10 (70%)		12/16 (75%)
Edema	3/10 (30%)		5/16 (31.3%)
Fever	3/10 (30%)		3/16 (18.8%)
Non-Cardiac Chest Pain	2/10 (20%)		2/16 (12.5%)
General Disorders And Administration Site Conditions - Other, Pain At Port Site	3/10 (30%)		0/16 (0%)
Infections and infestations
Skin Infection	1/10 (10%)		1/16 (6.3%)
Upper Respiratory Infection	1/10 (10%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Bruising	0/10 (0%)		3/16 (18.8%)
Investigations
Platelet Count Decreased	6/10 (60%)		15/16 (93.8%)
Neutrophil Count Decreased	4/10 (40%)		15/16 (93.8%)
White Blood Cell Decreased	2/10 (20%)		8/16 (50%)
Weight Loss	0/10 (0%)		1/16 (6.3%)
Metabolism and nutrition disorders
Anorexia	2/10 (20%)		12/16 (75%)
Hypomagnesemia	1/10 (10%)		1/16 (6.3%)
Dehydration	2/10 (20%)		0/16 (0%)
Hypokalemia	0/10 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Myalgia	8/10 (80%)		3/16 (18.8%)
Generalized Muscle Weakness	3/10 (30%)		5/16 (31.3%)
Nervous system disorders
Dizziness	5/10 (50%)		4/16 (25%)
Peripheral Sensory Neuropathy	2/10 (20%)		5/16 (31.3%)
Dysgeusia	2/10 (20%)		2/16 (12.5%)
Headache	2/10 (20%)		0/16 (0%)
Psychiatric disorders
Depression	1/10 (10%)		1/16 (6.3%)
Insomnia	1/10 (10%)		1/16 (6.3%)
Renal and urinary disorders
Urinary Frequency	1/10 (10%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	6/10 (60%)		6/16 (37.5%)
Cough	3/10 (30%)		3/16 (18.8%)
Nasal Congestion	2/10 (20%)		1/16 (6.3%)
Epistaxis	2/10 (20%)		1/16 (6.3%)
Respiratory, Thoracic And Mediastinal Disorders - Other, Hemoptysis	1/10 (10%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Rash	2/10 (20%)		2/16 (12.5%)
Skin And Subcutaneous Tissue Disorders - Other, Ecchymosis	3/10 (30%)		0/16 (0%)
Dry Skin	0/10 (0%)		1/16 (6.3%)
Skin And Subcutaneous Tissue Disorders - Other, Petechiae	1/10 (10%)		1/16 (6.3%)
Vascular disorders
Hematoma	2/10 (20%)		0/16 (0%)
Hypotension	2/10 (20%)		0/16 (0%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.