Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00490776
• Collaborator: (none)
• Enrollment: 9
• Locations: 18
• Arm: 1
• Actual Duration (Months): 26.6
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study evaluated the safety and efficacy of LBH589B in adult participants with refractory/resistant Cutaneous T-Cell Lymphoma and prior Histone Deacetylase (HDAC) inhibitor therapy.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous T-Cell Lymphoma	Drug: Panobinostat	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oral LBH589 in Adult Patients With Cutaneous T-Cell Lymphoma Who Are Intolerant to or Have Progressed on or After Prior HDAC Inhibitor
• Actual Study Start Date: Jul 5, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 22, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat 20 mg Participants received panobinostat, 20 milligrams (mg), capsules, orally, thrice weekly on alternate Days 1, 3, and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression, and/or physician's discretion to discontinue the treatment.	Drug: Panobinostat; Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.; Other Names: LBH589

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT) [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.

Secondary Outcome Measures

1. Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA) [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - <90%); some evidence of disease remains.

2. Response Rate in Participants With Refractory CTCL Using Modified Skin Score [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.

3. Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation [From first dose of study drug up to disease progression or death (up to approximately 2 years)]

   Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + … + lesions 6 = Total sum of weighted score where Lesion 1: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 2: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 6: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA

4. ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells) [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-<90%); some evidence of disease remains.

5. Duration of Response (DOR) [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days.

6. Time to Response (TTR) [From first dose of study drug up to study completion (approximately 2 years)]

   TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR.

7. Progression-Free Survival (PFS) [From first dose of study drug up to disease progression or death, (up to approximately 2 years)]

   PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.

Eligibility Criteria

Criteria

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

Inclusion criteria:

1. Written informed consent obtained prior to any screening procedures

2. Age greater than or equal to 18 years old

3. Participants with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome (SS). Participants with SS who have bone marrow involvement are also eligible. Participants with transformed CTCL are eligible

4. Participants must have been treated with an HDAC inhibitor given for the treatment of CTCL. Participants must have had disease progression on or following treatment with an HDAC inhibitor. Participants are also eligible if they had an inadequate response to an HDAC inhibitor defined as stable disease as the best response after at least 3 months of therapy. Participants previously treated with an HDAC inhibitor are also eligible if they experienced intolerance due to adverse events.

5. Baseline multiple-gated acquisition scan (MUGA) or echocardiogram must have demonstrated left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal

6. ECOG performance status ≤ 2

Exclusion criteria:

1. Participants with a history of visceral disease including central nervous system (CNS) involvement (i.e. stage IVB CTCL). Note, participants who have SS with bone marrow involvement are eligible

2. Impaired cardiac function

3. Concomitant use of drugs with a risk of causing torsades de pointes

4. Participants who have received chemotherapy or any investigational drug or undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy

5. Less than 3 months since prior electron beam therapy

6. Women who are pregnant or breast feeding, or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham/ The Kirklin Clinic	Birmingham	Alabama	United States	35233
2	UCLA Medical Center School of Medicine/ Dpt of Hematology-Oncology	Los Angeles	California	United States	90095
3	University of Colorado Health Sciences Center/Anschutz Cancer Pavillion	Aurora	Colorado	United States	80010
4	Florida Academic Dermatology Centers	Miami	Florida	United States	33136
5	Medical College of Georgia	Augusta	Georgia	United States	30912
6	Rush Presbyterian Hospital/St. Luke's Medical Center	Chicago	Illinois	United States	60612
7	St. Louis University Cancer Cennter	Saint Louis	Missouri	United States	63110
8	Nebraska Medical Center	Omaha	Nebraska	United States	68198
9	Our Lady of Mercy Medical Center/Comprehensive Cancer Center	Bronx	New York	United States	10466
10	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
11	NYU Clinical Cancer Center	New York	New York	United States	10016
12	Wake University Health Sciences	Winston-Salem	North Carolina	United States	27157
13	University of Oklahoma-Tulsa	Tulsa	Oklahoma	United States	74104
14	Craig Okada	Portland	Oregon	United States	97239
15	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania	United States	15213
16	The Jones Clinic	Germantown	Tennessee	United States	38138
17	MD Anderson Cancer Center/University of Texas	Houston	Texas	United States	77030
18	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-102

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00490776
• Other Study ID Numbers: CLBH589B2212
• First Posted: Jun 25, 2007
• Last Update Posted: Aug 18, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Cutaneous T-Cell Lymphoma; adults; Mycosis Fungoides; Sézary Syndrome; CTCL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Panobinostat

Study Results

Participant Flow

Recruitment Details	A total of 9 participants were enrolled in the study at 8 investigative sites in the USA from 5 July 2007 to 15 June 2009. Recruitment was stopped on 15 June 2009 (early termination date) due to low prevalence of study population and slow accrual.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Period Title: Overall Study
STARTED	9
COMPLETED	0
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (13.29)
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT)
Description	ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

2. Secondary Outcome

Title	Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA)
Description	Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - <90%); some evidence of disease remains.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

3. Secondary Outcome

Title	Response Rate in Participants With Refractory CTCL Using Modified Skin Score
Description	Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

4. Secondary Outcome

Title	Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation
Description	Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + … + lesions 6 = Total sum of weighted score where Lesion 1: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 2: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]; Lesion 6: cm^2 x [1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA
Time Frame	From first dose of study drug up to disease progression or death (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

5. Secondary Outcome

Title	ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells)
Description	ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-<90%); some evidence of disease remains.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

7. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR.
Time Frame	From first dose of study drug up to study completion (approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

8. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.
Time Frame	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
Measure Participants	0

Adverse Events

Time Frame	Adverse event (AE): From the first dose of study drug up to 28 days after the last dose of study drug (up to approximately 2 years); Serious Adverse Event (SAE): From the first dose of study drug up to 4 weeks after the last dose of study drug (up to approximately 2 years)
Adverse Event Reporting Description	Safety population included all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Arm/Group Title	Panobinostat 20 mg
Arm/Group Description	Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.
All Cause Mortality
	Panobinostat 20 mg
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
Serious Adverse Events
	Panobinostat 20 mg
	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)
Blood and lymphatic system disorders
Thrombocytopenia	1/9 (11.1%)
Gastrointestinal disorders
Nausea	1/9 (11.1%)
Vomiting	1/9 (11.1%)
Infections and infestations
Pneumonia	1/9 (11.1%)
Sepsis	1/9 (11.1%)
Metabolism and nutrition disorders
Hyperkalaemia	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Panobinostat 20 mg
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anaemia	1/9 (11.1%)
Lymphopenia	1/9 (11.1%)
Neutropenia	3/9 (33.3%)
Thrombocytopenia	5/9 (55.6%)
Cardiac disorders
Sinus tachycardia	1/9 (11.1%)
Ear and labyrinth disorders
Ear pruritus	1/9 (11.1%)
Eye disorders
Dry eye	1/9 (11.1%)
Eye irritation	1/9 (11.1%)
Lacrimation increased	1/9 (11.1%)
Vision blurred	1/9 (11.1%)
Gastrointestinal disorders
Constipation	1/9 (11.1%)
Diarrhoea	5/9 (55.6%)
Dry mouth	2/9 (22.2%)
Dyspepsia	1/9 (11.1%)
Dysphagia	1/9 (11.1%)
Gastrooesophageal reflux disease	1/9 (11.1%)
Gingival bleeding	1/9 (11.1%)
Haematochezia	1/9 (11.1%)
Nausea	6/9 (66.7%)
Stomatitis	1/9 (11.1%)
Toothache	1/9 (11.1%)
Vomiting	3/9 (33.3%)
General disorders
Asthenia	1/9 (11.1%)
Fatigue	4/9 (44.4%)
Gait disturbance	2/9 (22.2%)
Oedema peripheral	2/9 (22.2%)
Pain	1/9 (11.1%)
Pyrexia	2/9 (22.2%)
Thirst	1/9 (11.1%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/9 (11.1%)
Infections and infestations
Hordeolum	1/9 (11.1%)
Influenza	1/9 (11.1%)
Nasopharyngitis	1/9 (11.1%)
Oral candidiasis	1/9 (11.1%)
Postoperative wound infection	1/9 (11.1%)
Respiratory tract infection	1/9 (11.1%)
Sinusitis	1/9 (11.1%)
Staphylococcal skin infection	1/9 (11.1%)
Urinary tract infection	1/9 (11.1%)
Pneumonia	1/9 (11.1%)
Sepsis	1/9 (11.1%)
Injury, poisoning and procedural complications
Postoperative fever	1/9 (11.1%)
Procedural pain	1/9 (11.1%)
Investigations
Alanine aminotransferase increased	1/9 (11.1%)
Aspartate aminotransferase increased	1/9 (11.1%)
Blood thyroid stimulating hormone increased	1/9 (11.1%)
Electrocardiogram QT prolonged	1/9 (11.1%)
Lymph node palpable	1/9 (11.1%)
Weight decreased	3/9 (33.3%)
Metabolism and nutrition disorders
Decreased appetite	3/9 (33.3%)
Dehydration	1/9 (11.1%)
Hyperkalaemia	1/9 (11.1%)
Hyperphosphataemia	1/9 (11.1%)
Hypertriglyceridaemia	1/9 (11.1%)
Hyponatraemia	1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthritis	1/9 (11.1%)
Back pain	2/9 (22.2%)
Groin pain	1/9 (11.1%)
Nervous system disorders
Dizziness	1/9 (11.1%)
Dysgeusia	3/9 (33.3%)
Psychiatric disorders
Insomnia	1/9 (11.1%)
Renal and urinary disorders
Renal injury	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/9 (22.2%)
Nasal mucosal disorder	1/9 (11.1%)
Oropharyngeal pain	1/9 (11.1%)
Skin and subcutaneous tissue disorders
Drug eruption	1/9 (11.1%)
Pruritus	2/9 (22.2%)
Rash	1/9 (11.1%)
Skin burning sensation	1/9 (11.1%)
Skin induration	1/9 (11.1%)
Vascular disorders
Hypotension	1/9 (11.1%)
Lymphorrhoea	1/9 (11.1%)

Limitations/Caveats

The study was terminated early due to low accrual, no formal efficacy analyses were conducted for this study.

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 (i.e., data from all sites) in the clinical trial.