Efficacy and Safety of Panobinostat (LBH589) in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00880269
• Collaborator: (none)
• Enrollment: 59
• Locations: 40
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study was to evaluate the efficacy and safety of single agent oral panobinostat in patients who have refractory de novo or refractory secondary AML.

Condition or Disease	Intervention/Treatment	Phase
Refractory Leukemia; Acute Myelogenous Leukemia	Drug: Panobinostat/LBH589	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oral Single Agent Panobinostat in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Panobinostat/LBH589
Experimental: 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.	Drug: Panobinostat/LBH589

Outcome Measures

Primary Outcome Measures

1. Best Response as Per Investigator Assessment by Stratum (FAS) [6 cycles of treatment with a 28-day treatment cycle (Day 168)]

   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.

Secondary Outcome Measures

1. Partial Response Measured in Stratum A and B [6 treatment cycles (28-day/treatment cycle)]

   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)

2. Time to Remission Measured in Stratum A and B [6 treatment cycles (28-day/treatment cycle)]

3. Duration of Remission Measured in Stratum A and B [6 treatment cycles (28-day/treatment cycle)]

4. Event-free Survival Measured in Stratum A and B [6 treatment cycles (28-day/treatment cycle)]

5. Overall Survival Measured in Stratum A and B [6 treatment cycles (28-day/treatment cycle)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)	Chicago	Illinois	United States	60637
2	Nebraska Methodist Hospital Nebraska Methodist Hospital(2)	Omaha	Nebraska	United States	68114
3	North Shore University Hospital North Shore Univ	Manhasset	New York	United States	10030
4	Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)	NY	New York	United States	10065
5	Oregon Health Sciences University Dept. of OHSU (2)	Portland	Oregon	United States	97239
6	University of Texas Southwestern Medical Center Dept of Simmons Cancer Center	Dallas	Texas	United States	75390
7	University of Texas/MD Anderson Cancer Center Dept of MD Anderson (14)	Houston	Texas	United States	77030-4009
8	Novartis Investigative Site	Gosford	New South Wales	Australia	2250
9	Novartis Investigative Site	Herston	Queensland	Australia	4029
10	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
11	Novartis Investigative Site	Fitzroy	Victoria	Australia	3065
12	Novartis Investigative Site	Parkville	Victoria	Australia	3002
13	Novartis Investigative Site	Prahran	Victoria	Australia	3181
14	Novartis Investigative Site	Brugge		Belgium	8000
15	Novartis Investigative Site	Gent		Belgium	9000
16	Novartis Investigative Site	Liege		Belgium	4000
17	Novartis Investigative Site	Bobigny Cedex		France	93009
18	Novartis Investigative Site	Montpellier cedex 5		France	34295
19	Novartis Investigative Site	Nantes		France	44035
20	Novartis Investigative Site	Paris Cedex 4		France	75181
21	Novartis Investigative Site	Toulouse cedex 9		France	31059
22	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
23	Novartis Investigative Site	Frankfurt		Germany	60590
24	Novartis Investigative Site	Leipzig		Germany	04103
25	Novartis Investigative Site	Roma	RM	Italy	00133
26	Novartis Investigative Site	Roma	RM	Italy	00161
27	Novartis Investigative Site	Udine	UD	Italy	33100
28	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06591
29	Novartis Investigative Site	Surquillo	Lima	Peru	34
30	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
31	Novartis Investigative Site	Barcelona		Spain	08041
32	Novartis Investigative Site	Bern		Switzerland	3010
33	Novartis Investigative Site	Zürich		Switzerland	8091
34	Novartis Investigative Site	Ankara		Turkey	06100
35	Novartis Investigative Site	Balcova / Izmir		Turkey	35340
36	Novartis Investigative Site	Aberdeen	Scotland	United Kingdom	AB25 2ZN
37	Novartis Investigative Site	Leeds	West Yorkshire	United Kingdom	LS9 7TF
38	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
39	Novartis Investigative Site	London		United Kingdom	SE5 9RS
40	Novartis Investigative Site	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00880269
• Other Study ID Numbers: CLBH589B2213; 2008-002983-32
• First Posted: Apr 13, 2009
• Last Update Posted: Feb 23, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Novartis Pharmaceuticals: Acute myeloid leukemia; AML; relapsed acute myeloid leukemia; refractory AML; refractory de novo AML; refractory secondary AML; secondary AML; AML following myelodysplastic syndrome (MDS); AML following antecedent hematological disorder (AHD); AML resistant to therapy
• Additional relevant MeSH terms: Leukemia; Neoplasm Metastasis; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Panobinostat

Study Results

Participant Flow

Recruitment Details	Participant flow is based on the full analysis set (FAS) which is the same as the safety set and includes one dose of the study drug.
Pre-assignment Detail	Although this study did not complete stage 2, it is considered as a completed study because it follows Simon's optimal two-stage design in each stratum (predefined in the protocol), the study can stop due to futility at the end of Stage 1 and not be considered as a terminated study.

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	32	27
Discontinued Treatment	32	27
COMPLETED	0	0
NOT COMPLETED	32	27

Baseline Characteristics

Arm/Group Title	Stratum A	Stratum B	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	32	27	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (12.13)	68.5 (7.75)	65.5 (10.65)
Gender (Count of Participants)
Female	20 62.5%	8 29.6%	28 47.5%
Male	12 37.5%	19 70.4%	31 52.5%

Outcome Measures

1. Primary Outcome

Title	Best Response as Per Investigator Assessment by Stratum (FAS)
Description	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.
Time Frame	6 cycles of treatment with a 28-day treatment cycle (Day 168)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	32	27
Complete remission rate (CR/CRi)	3.1 9.7%	7.4 27.4%
Complete remission (CR)	0 0%	3.7 13.7%
CR with incomplete blood count recovery (CRi)	3.1 9.7%	3.7 13.7%
Partial remission (PR)	0 0%	0 0%
Treatment failure	40.6 126.9%	40.7 150.7%
Unknown	56.3 175.9%	51.9 192.2%

2. Secondary Outcome

Title	Partial Response Measured in Stratum A and B
Description	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)
Time Frame	6 treatment cycles (28-day/treatment cycle)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Time to Remission Measured in Stratum A and B
Time Frame	6 treatment cycles (28-day/treatment cycle)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Duration of Remission Measured in Stratum A and B
Time Frame	6 treatment cycles (28-day/treatment cycle)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Event-free Survival Measured in Stratum A and B
Time Frame	6 treatment cycles (28-day/treatment cycle)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Overall Survival Measured in Stratum A and B
Time Frame	6 treatment cycles (28-day/treatment cycle)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Stratum A	Stratum B
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were followed for 28 days after last dose (Day 467).
Arm/Group Title	Stratum A		Stratum B
Arm/Group Description	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.		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.
All Cause Mortality
	Stratum A		Stratum B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stratum A		Stratum B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/32 (90.6%)		23/27 (85.2%)
Blood and lymphatic system disorders
Anaemia	1/32 (3.1%)		2/27 (7.4%)
Febrile neutropenia	5/32 (15.6%)		5/27 (18.5%)
Leukocytosis	1/32 (3.1%)		0/27 (0%)
Neutropenia	1/32 (3.1%)		0/27 (0%)
Thrombocytopenia	8/32 (25%)		8/27 (29.6%)
Cardiac disorders
Angina pectoris	0/32 (0%)		1/27 (3.7%)
Atrial fibrillation	1/32 (3.1%)		3/27 (11.1%)
Tachycardia	0/32 (0%)		1/27 (3.7%)
Congenital, familial and genetic disorders
Aplasia	1/32 (3.1%)		0/27 (0%)
Gastrointestinal disorders
Abdominal pain	1/32 (3.1%)		0/27 (0%)
Colitis	0/32 (0%)		1/27 (3.7%)
Diarrhoea	2/32 (6.3%)		3/27 (11.1%)
Gastrointestinal haemorrhage	1/32 (3.1%)		1/27 (3.7%)
Impaired gastric emptying	1/32 (3.1%)		0/27 (0%)
Mouth ulceration	0/32 (0%)		1/27 (3.7%)
Nausea	3/32 (9.4%)		2/27 (7.4%)
Rectal haemorrhage	1/32 (3.1%)		0/27 (0%)
Stomatitis	0/32 (0%)		1/27 (3.7%)
Vomiting	2/32 (6.3%)		1/27 (3.7%)
General disorders
Asthenia	1/32 (3.1%)		2/27 (7.4%)
Fatigue	3/32 (9.4%)		0/27 (0%)
General physical health deterioration	1/32 (3.1%)		0/27 (0%)
Pyrexia	5/32 (15.6%)		1/27 (3.7%)
Infections and infestations
Abdominal infection	1/32 (3.1%)		0/27 (0%)
Abscess limb	1/32 (3.1%)		0/27 (0%)
Bacterial infection	1/32 (3.1%)		1/27 (3.7%)
Bacterial sepsis	1/32 (3.1%)		0/27 (0%)
Diverticulitis	2/32 (6.3%)		0/27 (0%)
Escherichia infection	1/32 (3.1%)		0/27 (0%)
Escherichia urinary tract infection	1/32 (3.1%)		0/27 (0%)
Gastroenteritis viral	1/32 (3.1%)		0/27 (0%)
Influenza	0/32 (0%)		1/27 (3.7%)
Lower respiratory tract infection fungal	1/32 (3.1%)		0/27 (0%)
Neutropenic sepsis	2/32 (6.3%)		0/27 (0%)
Pneumonia	1/32 (3.1%)		0/27 (0%)
Pneumonia fungal	1/32 (3.1%)		0/27 (0%)
Pseudomonal sepsis	1/32 (3.1%)		0/27 (0%)
Pseudomonas infection	1/32 (3.1%)		0/27 (0%)
Pyelonephritis	1/32 (3.1%)		0/27 (0%)
Sepsis	2/32 (6.3%)		3/27 (11.1%)
Septic shock	2/32 (6.3%)		1/27 (3.7%)
Soft tissue infection	1/32 (3.1%)		0/27 (0%)
Staphylococcal sepsis	0/32 (0%)		1/27 (3.7%)
Streptococcal sepsis	0/32 (0%)		1/27 (3.7%)
Urinary tract infection	3/32 (9.4%)		0/27 (0%)
Injury, poisoning and procedural complications
Fall	1/32 (3.1%)		0/27 (0%)
Infusion related reaction	0/32 (0%)		1/27 (3.7%)
Subdural haematoma	1/32 (3.1%)		1/27 (3.7%)
Transfusion reaction	0/32 (0%)		1/27 (3.7%)
Investigations
Alanine aminotransferase increased	0/32 (0%)		1/27 (3.7%)
Aspartate aminotransferase increased	0/32 (0%)		1/27 (3.7%)
Blood creatinine increased	0/32 (0%)		1/27 (3.7%)
Electrocardiogram ST segment depression	0/32 (0%)		1/27 (3.7%)
Electrocardiogram T wave abnormal	0/32 (0%)		1/27 (3.7%)
General physical condition abnormal	1/32 (3.1%)		0/27 (0%)
Neutrophil count decreased	0/32 (0%)		1/27 (3.7%)
Platelet count decreased	1/32 (3.1%)		2/27 (7.4%)
Metabolism and nutrition disorders
Dehydration	0/32 (0%)		2/27 (7.4%)
Fluid overload	0/32 (0%)		1/27 (3.7%)
Hyperglycaemia	1/32 (3.1%)		0/27 (0%)
Hypokalaemia	2/32 (6.3%)		0/27 (0%)
Metabolic acidosis	0/32 (0%)		1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Bone pain	0/32 (0%)		1/27 (3.7%)
Groin pain	1/32 (3.1%)		0/27 (0%)
Muscular weakness	1/32 (3.1%)		0/27 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	1/32 (3.1%)		0/27 (0%)
Nervous system disorders
Convulsion	0/32 (0%)		1/27 (3.7%)
Headache	1/32 (3.1%)		0/27 (0%)
Lethargy	1/32 (3.1%)		0/27 (0%)
Loss of consciousness	1/32 (3.1%)		1/27 (3.7%)
Somnolence	1/32 (3.1%)		0/27 (0%)
Syncope	0/32 (0%)		1/27 (3.7%)
Psychiatric disorders
Completed suicide	1/32 (3.1%)		0/27 (0%)
Mental status changes	1/32 (3.1%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/32 (0%)		1/27 (3.7%)
Epistaxis	0/32 (0%)		1/27 (3.7%)
Respiratory failure	0/32 (0%)		1/27 (3.7%)
Vascular disorders
Circulatory collapse	1/32 (3.1%)		0/27 (0%)
Hypotension	0/32 (0%)		1/27 (3.7%)
Systolic hypertension	0/32 (0%)		1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Stratum A		Stratum B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/32 (100%)		26/27 (96.3%)
Blood and lymphatic system disorders
Anaemia	9/32 (28.1%)		0/27 (0%)
Febrile neutropenia	6/32 (18.8%)		0/27 (0%)
Neutropenia	3/32 (9.4%)		4/27 (14.8%)
Thrombocytopenia	12/32 (37.5%)		7/27 (25.9%)
Eye disorders
Dry eye	2/32 (6.3%)		0/27 (0%)
Gastrointestinal disorders
Abdominal pain	2/32 (6.3%)		3/27 (11.1%)
Abdominal pain upper	3/32 (9.4%)		1/27 (3.7%)
Aphthous stomatitis	2/32 (6.3%)		0/27 (0%)
Constipation	7/32 (21.9%)		4/27 (14.8%)
Diarrhoea	25/32 (78.1%)		15/27 (55.6%)
Dry mouth	3/32 (9.4%)		0/27 (0%)
Dyspepsia	2/32 (6.3%)		1/27 (3.7%)
Dysphagia	1/32 (3.1%)		2/27 (7.4%)
Flatulence	2/32 (6.3%)		0/27 (0%)
Gingival bleeding	4/32 (12.5%)		0/27 (0%)
Mouth haemorrhage	2/32 (6.3%)		0/27 (0%)
Mouth ulceration	2/32 (6.3%)		0/27 (0%)
Nausea	18/32 (56.3%)		14/27 (51.9%)
Odynophagia	0/32 (0%)		2/27 (7.4%)
Stomatitis	3/32 (9.4%)		1/27 (3.7%)
Vomiting	12/32 (37.5%)		8/27 (29.6%)
General disorders
Asthenia	4/32 (12.5%)		5/27 (18.5%)
Chills	2/32 (6.3%)		0/27 (0%)
Fatigue	10/32 (31.3%)		9/27 (33.3%)
Non-cardiac chest pain	2/32 (6.3%)		1/27 (3.7%)
Oedema peripheral	4/32 (12.5%)		3/27 (11.1%)
Pain	5/32 (15.6%)		2/27 (7.4%)
Pyrexia	16/32 (50%)		7/27 (25.9%)
Infections and infestations
Skin infection	2/32 (6.3%)		0/27 (0%)
Urinary tract infection	2/32 (6.3%)		0/27 (0%)
Investigations
Blood potassium decreased	2/32 (6.3%)		0/27 (0%)
Electrocardiogram QT prolonged	1/32 (3.1%)		3/27 (11.1%)
Neutrophil count decreased	2/32 (6.3%)		0/27 (0%)
Platelet count decreased	5/32 (15.6%)		1/27 (3.7%)
Weight decreased	4/32 (12.5%)		1/27 (3.7%)
White blood cell count decreased	2/32 (6.3%)		0/27 (0%)
Metabolism and nutrition disorders
Decreased appetite	10/32 (31.3%)		9/27 (33.3%)
Dehydration	4/32 (12.5%)		3/27 (11.1%)
Hyperglycaemia	0/32 (0%)		4/27 (14.8%)
Hyperuricaemia	0/32 (0%)		3/27 (11.1%)
Hypoalbuminaemia	2/32 (6.3%)		0/27 (0%)
Hypocalcaemia	4/32 (12.5%)		0/27 (0%)
Hypokalaemia	9/32 (28.1%)		2/27 (7.4%)
Hypomagnesaemia	3/32 (9.4%)		0/27 (0%)
Hypophosphataemia	1/32 (3.1%)		2/27 (7.4%)
Musculoskeletal and connective tissue disorders
Back pain	3/32 (9.4%)		1/27 (3.7%)
Bone pain	2/32 (6.3%)		1/27 (3.7%)
Muscular weakness	3/32 (9.4%)		1/27 (3.7%)
Neck pain	2/32 (6.3%)		0/27 (0%)
Pain in extremity	2/32 (6.3%)		2/27 (7.4%)
Nervous system disorders
Dizziness	0/32 (0%)		2/27 (7.4%)
Dysgeusia	3/32 (9.4%)		1/27 (3.7%)
Headache	3/32 (9.4%)		0/27 (0%)
Psychiatric disorders
Agitation	3/32 (9.4%)		0/27 (0%)
Anxiety	3/32 (9.4%)		1/27 (3.7%)
Insomnia	5/32 (15.6%)		2/27 (7.4%)
Mental status changes	2/32 (6.3%)		0/27 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	2/32 (6.3%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/32 (9.4%)		2/27 (7.4%)
Dysphonia	2/32 (6.3%)		0/27 (0%)
Dyspnoea	6/32 (18.8%)		1/27 (3.7%)
Epistaxis	4/32 (12.5%)		1/27 (3.7%)
Skin and subcutaneous tissue disorders
Petechiae	3/32 (9.4%)		0/27 (0%)
Rash	2/32 (6.3%)		0/27 (0%)
Skin lesion	2/32 (6.3%)		1/27 (3.7%)
Vascular disorders
Hypotension	3/32 (9.4%)		3/27 (11.1%)
Thrombophlebitis	2/32 (6.3%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.