Efficacy and Safety of Panobinostat (LBH589) in Patients... | NCT00880269

ID	Type	Description	Link
2008-002983-32	EudraCT Number

Label	Type	Description	Intervention Names
Stratum A	Experimental	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.	Drug: Panobinostat/LBH589
Stratum B	Experimental	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.	Drug: Panobinostat/LBH589

Name	Type	Description	Arm Group Labels	Other Names
Panobinostat/LBH589	Drug		Stratum A Stratum B

Measure	Description	Time Frame
Best Response as Per Investigator Assessment by Stratum (FAS)	Response to treatment was defined as complete remission rate (CRR). CRR is complete remission (CR) and morphologic CR with incomplete blood count recovery (residual neutropenia or thrombocytopenia) (CRi). To stop or to proceed with Stage 2 of a given stratum of the Simon's optimal 2-stage design was based on the number of patients with CR/CRi and a safety evaluation of the patients from Stage 1 in that stratum. If early results clearly indicated that the drug was not active or worthy of further investigation, enrollment of that particular stratum would be terminated. CR and CRi were assessed by the Investigator according to IWG response Criteria for AML (Cheson et al 2003). As per protocol we would continue to stage II if ≥ 4 patients out of 26 patients enrolled to stage I had a CR or a CRi. As per response observed there was only 1 patient with CR/CRi in stratum A and 2 patients with CR/CRi in Stratum B.	6 cycles of treatment with a 28-day treatment cycle (Day 168)

Measure	Description	Time Frame
Partial Response Measured in Stratum A and B	As predefined in the study's protocol, stage II was not pursued due to lack of activity (at end of stage I less than 4 patients in each stratum with CR/CRi)	6 treatment cycles (28-day/treatment cycle)
Time to Remission Measured in Stratum A and B

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent prior to study-specific screening procedures
Life expectancy of ≥ 60 days
Eastern Cooperative Group (ECOG) performance status ≤ 2
Refractory AML with confirmed initial diagnosis of de novo AML (excluding APL) - OR- Refractory AML with confirmed initial diagnosis of AML (excluding APL) secondary to AHD or MDS with either condition precedent to AML (MDS/AHD)
Negative serum pregnancy test (within 7 days of first dose)
Negative urine pregnancy test immediately prior to first dose

Exclusion Criteria:

Known HIV
Psychiatric disorder that interfered with ability to understand the study and give informed consent, and/or would impact study participation or follow-up
Concurrent use of medications that might prolong the QT interval or of inducing Torsade de Pointes
Female patients who were pregnant or breast-feeding or patients of childbearing potential who were not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug.
Male patients whose sexual partner(s) were women of childbearing potential who were not willing to use a double method of contraception, one of which included a condom, during the study and for 3 months after the end of treatment
Patient unable to swallow capsules
Patients with impaired gastrointestinal systems which might cause interference with digesting and absorbing panobinostat

Other Protocol-defined inclusion/exclusion criteria may apply

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)		Chicago	Illinois	60637	United States

Label	URL
Related Info	View source

ID	Title	Description
FG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
FG001	Stratum B

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Best Response as Per Investigator Assessment by Stratum (FAS)

Response to treatment was defined as complete remission rate (CRR). CRR is complete remission (CR) and morphologic CR with incomplete blood count recovery (residual neutropenia or thrombocytopenia) (CRi). To stop or to proceed with Stage 2 of a given stratum of the Simon's optimal 2-stage design was based on the number of patients with CR/CRi and a safety evaluation of the patients from Stage 1 in that stratum. If early results clearly indicated that the drug was not active or worthy of further investigation, enrollment of that particular stratum would be terminated. CR and CRi were assessed by the Investigator according to IWG response Criteria for AML (Cheson et al 2003). As per protocol we would continue to stage II if ≥ 4 patients out of 26 patients enrolled to stage I had a CR or a CRi. As per response observed there was only 1 patient with CR/CRi in stratum A and 2 patients with CR/CRi in Stratum B.

Full analysis set (FAS) is the same as the Safety set and includes all patients who received at least one dose of study drug. The FAS was used for final efficacy analyses.

Posted

Number

Percentage of Participants

6 cycles of treatment with a 28-day treatment cycle (Day 168)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG00032 OG00127

Title

Denominators

Categories

Complete remission rate (CR/CRi)

Title	Measurements
	OG0003.1 OG0017.4

Complete remission (CR)

Title	Measurements
	OG000

Secondary

Partial Response Measured in Stratum A and B

As predefined in the study's protocol, stage II was not pursued due to lack of activity (at end of stage I less than 4 patients in each stratum with CR/CRi)

No secondary analyses were performed since study enrollment was stopped early at stage 1 for lack of evidence of activity.

Posted

6 treatment cycles (28-day/treatment cycle)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG000

Secondary

Time to Remission Measured in Stratum A and B

No secondary analyses were performed since study enrollment was stopped early at stage 1 for lack of evidence of activity.

Posted

6 treatment cycles (28-day/treatment cycle)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG000

Secondary

Duration of Remission Measured in Stratum A and B

No secondary analyses were performed since study enrollment was stopped early at stage 1 for lack of evidence of activity.

Posted

6 treatment cycles (28-day/treatment cycle)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG000

Secondary

Event-free Survival Measured in Stratum A and B

No secondary analyses were performed since study enrollment was stopped early at stage 1 for lack of evidence of activity.

Posted

6 treatment cycles (28-day/treatment cycle)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG000

Secondary

Overall Survival Measured in Stratum A and B

No secondary analyses were performed since study enrollment was stopped early at stage 1 for lack of evidence of activity.

Posted

6 treatment cycles (28-day/treatment cycle)

ID	Title	Description
OG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
OG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0012 affected27 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0005 affected32 at risk EG0015 affected27 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0008 affected32 at risk EG0018 affected27 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0013 affected27 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Aplasia	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Colitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0013 affected27 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0011 affected27 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0012 affected27 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0012 affected27 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0005 affected32 at risk EG0011 affected27 at risk
Abdominal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Abscess limb	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Bacterial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0011 affected27 at risk
Bacterial sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Escherichia infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Lower respiratory tract infection fungal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Neutropenic sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Pneumonia fungal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Pseudomonas infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0013 affected27 at risk
Septic shock	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Soft tissue infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Streptococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0011 affected27 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Electrocardiogram ST segment depression	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Electrocardiogram T wave abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
General physical condition abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Neutrophil count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0012 affected27 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0012 affected27 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Lethargy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Loss of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0011 affected27 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Completed suicide	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Circulatory collapse	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0010 affected27 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk
Systolic hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0011 affected27 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0009 affected32 at risk EG0010 affected27 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0006 affected32 at risk EG0010 affected27 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0014 affected27 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00012 affected32 at risk EG0017 affected27 at risk
Dry eye	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0013 affected27 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected32 at risk EG0014 affected27 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00025 affected32 at risk EG00115 affected27 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0012 affected27 at risk
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0010 affected27 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00018 affected32 at risk EG00114 affected27 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0012 affected27 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00012 affected32 at risk EG0018 affected27 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0015 affected27 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00010 affected32 at risk EG0019 affected27 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0013 affected27 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0005 affected32 at risk EG0012 affected27 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG00016 affected32 at risk EG0017 affected27 at risk
Skin infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Blood potassium decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0013 affected27 at risk
Neutrophil count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0005 affected32 at risk EG0011 affected27 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0011 affected27 at risk
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00010 affected32 at risk EG0019 affected27 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0013 affected27 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0014 affected27 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0013 affected27 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0010 affected27 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0009 affected32 at risk EG0012 affected27 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected32 at risk EG0012 affected27 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0012 affected27 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected32 at risk EG0012 affected27 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0011 affected27 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0005 affected32 at risk EG0012 affected27 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0012 affected27 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected32 at risk EG0011 affected27 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected32 at risk EG0011 affected27 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0010 affected27 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0011 affected27 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0003 affected32 at risk EG0013 affected27 at risk
Thrombophlebitis	Vascular disorders	MedDRA	Systematic Assessment	EG0002 affected32 at risk EG0010 affected27 at risk

ID	Term
D007938	Leukemia
D015470	Leukemia, Myeloid, Acute

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007951	Leukemia, Myeloid

ID	Term
D006877	Hydroxamic Acids
D006898	Hydroxylamines
D000588	Amines
D009930	Organic Chemicals
D006880	Hydroxy Acids
D002264	Carboxylic Acids
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.
BG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stratum A	patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week.			29	32	32	32
EG001	Stratum B	patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week.			23	27	26	27