Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL

• Sponsor: Kyowa Kirin, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01728805
• Collaborator: (none)
• Enrollment: 372
• Locations: 73
• Arms: 2
• Actual Duration (Months): 99.5
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or refractory CTCL.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous T-Cell Lymphoma	Biological: KW-0761; Drug: Vorinostat	Phase 3

Detailed Description

Phase 3 randomized study to compare the progression free survival of subjects with relapsed/refractory CTCL who receive KW-0761 versus those who receive vorinostat. Subjects who progress on vorinostat will be allowed to cross over to KW-0761 upon progression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 372 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 (Mogamulizumab) Versus Vorinostat in Subjects With Previously Treated Cutaneous T-Cell Lymphoma
• Actual Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Feb 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KW-0761 anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)	Biological: KW-0761; 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression; Other Names: mogamulizumab POTELIGEO®
Active Comparator: Vorinostat vorinostat 400 mg once daily	Drug: Vorinostat; Other Names: 400 mg orally daily ZOLINZA®

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [From date of randomization at every visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months]

   Progression was defined as follows, based on Olsen (2011): Lymph nodes: ≥ 50% increase in SPD from baseline of lymph nodes, any new node > 1.5 cm in the long axis or > 1 cm in the short axis if 1-1.5 cm in the long axis that is proven to be N3 histologically, or > 50% increase from nadir in SPD of lymph nodes in those with PR Skin: ≥ 25% increase in skin disease from baseline, new tumors (T3) in patients with T1, T2 or T4 only skin disease, or in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score Blood: B0 to B2, > 50% increase from baseline and at least 5,000 neoplastic cells/μL36, or > 50% increase from nadir and at least 5,000 neoplastic cells/μL Viscera: > 50% increase in size (SPD) of any organs involved at baseline, new organ involvement, or > 50% increase from nadir in the size (SPD) of any previous organ involvement in those with PR

Secondary Outcome Measures

1. Overall Response Rate [at the end of cycle 1 (26-28 days), and then every other cycle in Year 1 (cycle 3, 5, 7, 9, 11, 13), and every 16 weeks (cycle 17, 21, etc.) in Year 2 and beyond until progression up to 36 months]

   The ORR was defined as the count of subjects who had a confirmed CR or PR, defined as documented CR or PR per Global Composite Response Score that was confirmed by a subsequent observation at least 4 weeks later. Overall Response Rate was determined based on the response in all compartments (lymph nodes, skin, peripheral blood, and viscera), referencing Olsen, 2011 as follows: Complete Response (CR) = complete disappearance of all clinical evidence of disease; Partial Response (PR) = regression of measurable disease; Stable Disease (SD) = failure to attain CR, PR, or PD; Progressive Disease (PD) = PD in any compartment; Relapse = recurrence of disease in prior CR in any compartment.

2. Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score [Cycle 1, 3, and 5]

   Skindex-29 rates 29 items assessing 3 domains (emotions, symptoms, & functioning) on a linear scale from 0 (never) to all the time (100). Higher scores = higher impact of skin disease. FACT-G rates 27 items in 4 domains (physical well-being, social/family well-being, emotional well-being, functional well-being) on a 5-point scale from 0 (not at all) to 4 (very much). Higher scores = better QoL. EuroQoL lvl 3 (Eq-5D-3L) rates mobility, self-care, usual activities, pain/discomfort and anxiety/depression on 3 levels - no problems, some problems, extreme problems. Score is calculated using a set of item weights to derive a single score ranging from -0.109 to 1, with 1 representing full health. LS mean (and 95% CI) of the overall change from baseline across time points through 6-month assessment (including End of Cycles 1, 3, and 5 time points only) are calculated from MMRM with treatment, disease type, disease stage, and region as fixed effects and baseline score as a covariate.

3. Pruritis Evaluation [Cycle 1, 3, and 5]

   The Itchy QoL is a validated pruritus specific quality of life instrument. It includes 22 pruritus-specific questions covering three major domains: symptoms, functioning, and emotions. The scale ranges from Never (1) to All The Time (5). The subscale scores consist of the average of the responses to the items in a given subscale. The overall score is the average of the responses to all items. Higher Itchy QoL scores indicate worse quality of life. LS mean (and 95% CI) of the overall change from baseline across time points through 6-month assessment (including End of Cycles 1, 3, and 5 time points only) are calculated from MMRM with treatment, disease type, disease stage, and region as fixed effects and baseline score as a covariate.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male and female subjects ≥ 18 years of age at the time of enrollment, except in Japan where subjects must be ≥ 20 years of age at the time of enrollment

• Histologically confirmed diagnosis of mycosis fungoides (MF) or Sezary Syndrome (SS)

• Stage IB, II-A, II-B, III and IV

• Subjects who had failed at least one prior course of systemic therapy. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy

• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study entry

• Resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0)

• Adequate hematological, renal and hepatic function

• Subjects previously treated with anti-CD4 antibody or alemtuzumab were eligible provided their CD4+ cell counts were ≥ 200/mm3

• Subjects with mycosis fungoides (MF) and a known history of non-complicated staphylococcus infection/colonization were eligible provided they continued to receive stable doses of prophylactic antibiotics

• Women of childbearing potential (WOCBP) must have had a negative pregnancy test within 7 days of receiving study medication

• WOCBP and male subjects as well as their female partners of childbearing potential must have agreed to use effective contraception throughout the study and for 3 months after the last dose of KW-0761

Exclusion Criteria:

• Prior treatment with KW-0761 or vorinostat.

• Large cell transformation. However, subjects with a history of LCT but without current aggressive disease and no current evidence of LCT on pathology in skin and lymph nodes would be eligible.

• Diagnosed with a malignancy in the past two years. However, subjects with non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA of <0.1 ng/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast within the past two years could enroll as long as there was no current evidence of disease.

• Clinical evidence of central nervous system (CNS) metastasis.

• Psychiatric illness, disability or social situation that would have compromised the subject's safety or ability to provide consent, or limited compliance with study requirements.

• Significant uncontrolled intercurrent illness

• Known or tested positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B or hepatitis C.

• Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, and had no active signs of active infection, and whose last active infection was more than 6 months ago, could enter the study, and should have continued to take the prescribed medication for the duration of the study.

• Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.

• Known active autoimmune disease were excluded. (For example, Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis).

• Was pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.

• History of allogeneic transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Birmingham	Birmingham	Alabama	United States	35233
2	Banner MD Anderson	Gilbert	Arizona	United States	85234
3	City of Hope National Medical Center	Duarte	California	United States	91010
4	UCLA Medical Center	Los Angeles	California	United States	90095
5	Stanford Medical Center	Stanford	California	United States	94305
6	University of Colorado	Aurora	Colorado	United States	80045
7	Yale University School of Medicine - Yale Cancer Center	New Haven	Connecticut	United States	06520
8	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
9	The Winship Cancer Institute (Emory University)	Atlanta	Georgia	United States	30322
10	Northwestern University	Chicago	Illinois	United States	60611
11	Indiana University	Indianapolis	Indiana	United States	46202
12	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
13	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	Boston Medical Center, Department of Medicine, Section of Hem/Onc	Boston	Massachusetts	United States	02118
16	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
17	University of Michigan	Ann Arbor	Michigan	United States	48109
18	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
19	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Universal Dermatology, PLLC	Fairport	New York	United States	14450
21	Columbia Presbyterian	New York	New York	United States	10037
22	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
23	University of Rochester School of Medicine	Rochester	New York	United States	14642
24	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
25	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
26	Ohio State University	Columbus	Ohio	United States	43210
27	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
28	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
29	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania	United States	15208
30	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
31	M.D.Anderson Cancer Center	Houston	Texas	United States	77030
32	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
33	University of Washington	Seattle	Washington	United States	98109
34	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53266
35	Westmead Hospital	Westmead	New South Wales	Australia	2145
36	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
37	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
38	Parkville Cancer Clinical Trials Unit	Melbourne	Victoria	Australia	3000
39	Aarhus University Hospital	Aarhus		Denmark	8000
40	CHU de Nantes	Nantes		France	44093
41	Hôpital Saint Louis	Paris		France	75010
42	CHU Bordeaux - Hopital Haut-Leveque	Pessac		France	33604
43	Centre Hospitalier Lyon Sud	Pierre-Benite Cedex		France	69495
44	University Medical Centre Mannheim	Mannheim		Germany	D-68167
45	University Hospital Muenster	Muenster		Germany	48149
46	Institute of Hematology and Oncology Lorenzo e Ariosto Seràgnoli, University of Bologna	Bologna		Italy	40138
47	Universita degli Studi di Torino	Turin		Italy	10124
48	Nagoya City University Hospital	Nagoya-shi	Aichi	Japan	467-8602
49	Fukushima Medical University Hospital	Fukushima-shi	Fukushima	Japan	960-1295
50	Gunma University Hospital	Maebashi-shi	Gunma	Japan	371-8511
51	Hiroshima University Hospital	Hiroshima-shi	Hiroshima	Japan	734-8551
52	Asahikawa Medical University Hospital	Asahikawa	Hokkaido	Japan	078-8510
53	Imamura Bun-in Hospital	Kagoshima-shi	Kagoshima	Japan	890-0064
54	Yokohama City University Hospital	Yokohama-shi	Kanagawa	Japan	236-0004
55	Kochi Medical School Hospital	Nankoku-shi	Kochi	Japan	783-8505
56	Mie University Hospital	Tsu-shi	Mie	Japan	514-8507
57	Tohoku University Hospital	Sendai-shi	Miyagi	Japan	980-8574
58	Shinshu University Hospital	Matsumoto-shi	Nagano	Japan	390-8621
59	Okayama University Hospital	Okayama-shi	Okayama	Japan	700-8558
60	Kansai Medical University Hospital	Hirakata-shi	Osaka	Japan	571-1191
61	Osaka University Hospital	Suita-shi	Osaka	Japan	565-0871
62	Hamamatsu University Hospital	Hamamatsu-shi	Shizuoka	Japan	431-3192
63	The University of Tokyo Hospital	Bunkyo-ku	Tokyo	Japan	113-8655
64	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
65	Tokyo Metropolitan Tama Medical Center	Fuchu-shi	Tokyo	Japan	183-8524
66	Japanese Foundation for Cancer Research	Koto-ku	Tokyo	Japan	135-8550
67	Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)	Leiden		Netherlands	2300RC
68	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
69	Hospital Universitario de Salamanca	Salamanca		Spain	37007
70	University Hospital Zurich	Zurich		Switzerland	8091
71	The Christie Hospital Foundation NHS Trust	Manchester	Greater Manchester	United Kingdom	M20 4BX
72	University Hospital Birmingham	Birmingham		United Kingdom	B15 2TH
73	Guys & St. Thomas NHS Trust	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• Kyowa Kirin, Inc.

Investigators

• Study Director: Dmitri O. Grebennik, MD, Kyowa Kirin, Inc.

Study Documents (Full-Text)

• Study Protocol - May 31, 2018
• Statistical Analysis Plan - Nov 22, 2016

More Information

Publications

None provided.

• Responsible Party: Kyowa Kirin, Inc.
• ClinicalTrials.gov Identifier: NCT01728805
• Other Study ID Numbers: 0761-010
• First Posted: Nov 20, 2012
• Last Update Posted: Jul 28, 2022
• Last Verified: Apr 1, 2021

• Keywords provided by Kyowa Kirin, Inc.: Cutaneous T-Cell Lymphoma (CTCL); myocis fungoides (MF); Sezary Syndrome (SS)
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Vorinostat; Mogamulizumab

Study Results

Participant Flow

Arm/Group Title	KW-0761	Vorinostat	Vorinostat Original Then Crossover to KW-0761
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat	Subjects who were randomized to vorinostat could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.
Period Title: Randomization Period
STARTED	186	186	0
COMPLETED	186	186	0
NOT COMPLETED	0	0	0
Period Title: Randomization Period
STARTED	0	0	136
COMPLETED	0	0	136
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	KW-0761	Vorinostat	Total
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat	Total of all reporting groups
Overall Participants	186	186	372
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	99 53.2%	89 47.8%	188 50.5%
>=65 years	87 46.8%	97 52.2%	184 49.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62.8	63.3	63.0
Sex: Female, Male (Count of Participants)
Female	77 41.4%	79 42.5%	156 41.9%
Male	109 58.6%	107 57.5%	216 58.1%
Race/Ethnicity, Customized (Count of Participants)
White	125 67.2%	135 72.6%	260 69.9%
Other	37 19.9%	26 14%	63 16.9%
Not Reported	24 12.9%	25 13.4%	49 13.2%
Region of Enrollment (participants) [Number]
Netherlands	0 0%	2 1.1%	2 0.5%
United States	98 52.7%	103 55.4%	201 54%
Japan	9 4.8%	6 3.2%	15 4%
Denmark	1 0.5%	2 1.1%	3 0.8%
Italy	14 7.5%	12 6.5%	26 7%
United Kingdom	16 8.6%	14 7.5%	30 8.1%
France	23 12.4%	24 12.9%	47 12.6%
Australia	9 4.8%	7 3.8%	16 4.3%
Switzerland	2 1.1%	2 1.1%	4 1.1%
Germany	5 2.7%	6 3.2%	11 3%
Spain	9 4.8%	8 4.3%	17 4.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	Progression was defined as follows, based on Olsen (2011): Lymph nodes: ≥ 50% increase in SPD from baseline of lymph nodes, any new node > 1.5 cm in the long axis or > 1 cm in the short axis if 1-1.5 cm in the long axis that is proven to be N3 histologically, or > 50% increase from nadir in SPD of lymph nodes in those with PR Skin: ≥ 25% increase in skin disease from baseline, new tumors (T3) in patients with T1, T2 or T4 only skin disease, or in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score Blood: B0 to B2, > 50% increase from baseline and at least 5,000 neoplastic cells/μL36, or > 50% increase from nadir and at least 5,000 neoplastic cells/μL Viscera: > 50% increase in size (SPD) of any organs involved at baseline, new organ involvement, or > 50% increase from nadir in the size (SPD) of any previous organ involvement in those with PR
Time Frame	From date of randomization at every visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761	Vorinostat
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat
Measure Participants	186	186
Rate (%) of Being Alive w/o Progression at 6 mos.	55.3	28.8
Rate (%) of Being Alive w/o Progression at 12 mos.	38.3	15.3
Rate (%) of Being Alive w/o Progression at 18 mos.	28.0	7.2
Rate (%) of Being Alive w/o Progression at 24 mos.	14.1	7.2
Rate (%) of Being Alive w/o Progression at 30 mos.	4.7	7.2

2. Secondary Outcome

Title	Overall Response Rate
Description	The ORR was defined as the count of subjects who had a confirmed CR or PR, defined as documented CR or PR per Global Composite Response Score that was confirmed by a subsequent observation at least 4 weeks later. Overall Response Rate was determined based on the response in all compartments (lymph nodes, skin, peripheral blood, and viscera), referencing Olsen, 2011 as follows: Complete Response (CR) = complete disappearance of all clinical evidence of disease; Partial Response (PR) = regression of measurable disease; Stable Disease (SD) = failure to attain CR, PR, or PD; Progressive Disease (PD) = PD in any compartment; Relapse = recurrence of disease in prior CR in any compartment.
Time Frame	at the end of cycle 1 (26-28 days), and then every other cycle in Year 1 (cycle 3, 5, 7, 9, 11, 13), and every 16 weeks (cycle 17, 21, etc.) in Year 2 and beyond until progression up to 36 months

Outcome Measure Data

Analysis Population Description

The total number of patients analyzed are further broken out by disease type [mycosis fungoides (MF) and Sezary Syndrome (SS)]

Arm/Group Title	KW-0761	Vorinostat
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat
Measure Participants	186	186
All Subjects ORR (confirmed CR + PR)	52 28%	9 4.8%
Disease Type = MF ORR (confirmed CR + PR)	22 11.8%	7 3.8%
Disease Type = SS ORR (confirmed CR + PR)	30 16.1%	2 1.1%

3. Secondary Outcome

Title	Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score
Description	Skindex-29 rates 29 items assessing 3 domains (emotions, symptoms, & functioning) on a linear scale from 0 (never) to all the time (100). Higher scores = higher impact of skin disease. FACT-G rates 27 items in 4 domains (physical well-being, social/family well-being, emotional well-being, functional well-being) on a 5-point scale from 0 (not at all) to 4 (very much). Higher scores = better QoL. EuroQoL lvl 3 (Eq-5D-3L) rates mobility, self-care, usual activities, pain/discomfort and anxiety/depression on 3 levels - no problems, some problems, extreme problems. Score is calculated using a set of item weights to derive a single score ranging from -0.109 to 1, with 1 representing full health. LS mean (and 95% CI) of the overall change from baseline across time points through 6-month assessment (including End of Cycles 1, 3, and 5 time points only) are calculated from MMRM with treatment, disease type, disease stage, and region as fixed effects and baseline score as a covariate.
Time Frame	Cycle 1, 3, and 5

Outcome Measure Data

Analysis Population Description

The number of subjects analyzed in each row is the number of subjects with values at baseline and the specified post-baseline timepoint.

Arm/Group Title	KW-0761	Vorinostat
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat
Measure Participants	186	186
Skindex-29 Across 6-month Assessment	-12.6	-6.0
FACT-G Across 6-month Assessment	4.6	-2.3
EQ-5D-3L Across 6-month Assessment	0.06	0.02

4. Secondary Outcome

Title	Pruritis Evaluation
Description	The Itchy QoL is a validated pruritus specific quality of life instrument. It includes 22 pruritus-specific questions covering three major domains: symptoms, functioning, and emotions. The scale ranges from Never (1) to All The Time (5). The subscale scores consist of the average of the responses to the items in a given subscale. The overall score is the average of the responses to all items. Higher Itchy QoL scores indicate worse quality of life. LS mean (and 95% CI) of the overall change from baseline across time points through 6-month assessment (including End of Cycles 1, 3, and 5 time points only) are calculated from MMRM with treatment, disease type, disease stage, and region as fixed effects and baseline score as a covariate.
Time Frame	Cycle 1, 3, and 5

Outcome Measure Data

Analysis Population Description

The number of participants analyzed were subjects with values at baseline and post-baseline.

Arm/Group Title	KW-0761	Vorinostat
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression	vorinostat 400 mg once daily Vorinostat
Measure Participants	166	175
Least Squares Mean (95% Confidence Interval) [score on a scale]	-0.5	-0.4

Adverse Events

Time Frame	All subjects were assessed regularly for potential occurrence of adverse events from the time of signing the informed consent until 90 days after the last dose or initiation of alternative therapy, whichever came first, assessed up to 36 months.
Adverse Event Reporting Description	The following tables are based on the safety analysis set (all subjects who received at least one dose, even a partial dose, of the assigned study agent). Two subjects randomized to the mogamulizumab arm withdrew consent prior to receiving the first dose subsequently did not receive study treatment, bringing the number from 186 to 184. One subject crossed over from vorinostat to mogamulizumab but discontinued before receiving treatment, bringing the number from 136 to 135.
Arm/Group Title	KW-0761		Vorinostat		Vorinostat Original Then Crossover to KW-0761
Arm/Group Description	anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) KW-0761: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression		vorinostat 400 mg once daily Vorinostat		Subjects who were randomized to vorinostat could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.
All Cause Mortality
	KW-0761		Vorinostat		Vorinostat Original Then Crossover to KW-0761
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/184 (21.7%)		47/186 (25.3%)		32/135 (23.7%)
Serious Adverse Events
	KW-0761		Vorinostat		Vorinostat Original Then Crossover to KW-0761
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/184 (37.5%)		46/186 (24.7%)		40/135 (29.6%)
Blood and lymphatic system disorders
Anaemia	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Anaemia Haemolytic Autoimmune	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Febrile Neutropenia	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Haemolytic Anaemia	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Neutropenia	0/184 (0%)	0	2/186 (1.1%)	2	0/135 (0%)	0
Thrombocytopenia	0/184 (0%)	0	3/186 (1.6%)	4	0/135 (0%)	0
Cardiac disorders
Acute Myocardial Infarction	1/184 (0.5%)	1	0/186 (0%)	0	1/135 (0.7%)	1
Angina Pectoris	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Angina Unstable	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Atrial Fibrillation	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Cardiac Failure	1/184 (0.5%)	2	0/186 (0%)	0	0/135 (0%)	0
Left Ventricular Hypertrophy	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Myocarditis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Supraventricular Tachycardia	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Ear and labyrinth disorders
Ear Pain	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Eye disorders
Lens Dislocation	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Retinal Vein Occlusion	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Gastrointestinal disorders
Abdominal Pain	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Abdominal Pain Upper	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Anal Fistula	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Colitis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Constipation	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Diarrhoea	1/184 (0.5%)	1	1/186 (0.5%)	1	1/135 (0.7%)	1
Gastric Haemorrhage	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Gastrointestinal Haemorrhage	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Ileitis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Inguinal Hernia	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Intestinal Obstruction	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Large Intestinal Ulcer Haemorrhage	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Lip Swelling	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Nausea	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Stomatitis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	3
Vomiting	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
General disorders
Asthenia	0/184 (0%)	0	2/186 (1.1%)	2	1/135 (0.7%)	1
Chest Discomfort	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Chest Pain	0/184 (0%)	0	0/186 (0%)	0	2/135 (1.5%)	2
Death	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Device Failure	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Disease Progression	4/184 (2.2%)	4	1/186 (0.5%)	1	0/135 (0%)	0
Facial Pain	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Fatigue	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
General Physical Health Deterioration	1/184 (0.5%)	1	1/186 (0.5%)	2	0/135 (0%)	0
Hypothermia	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Localised Oedema	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Oedema	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Oedema Peripheral	0/184 (0%)	0	1/186 (0.5%)	1	2/135 (1.5%)	3
Pyrexia	8/184 (4.3%)	9	1/186 (0.5%)	1	2/135 (1.5%)	5
Hepatobiliary disorders
Autoimmune Hepatitis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Cholangitis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Cholecystitis Acute	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Hepatic Failure	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Hepatitis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Hepatitis Acute	1/184 (0.5%)	1	0/186 (0%)	0	1/135 (0.7%)	1
Hepatocellular Injury	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Immune system disorders
Contrast Media Allergy	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Drug Hypersensitivity	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Hypersensitivity	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Infections and infestations
Abscess Limb	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Appendicitis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Arthritis Bacterial	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Atypical Pneumonia	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Bacteraemia	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Bronchitis	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Bronchopneumonia	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Cellulitis	5/184 (2.7%)	5	6/186 (3.2%)	6	3/135 (2.2%)	3
Cytomegalovirus Infection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Device Related Infection	0/184 (0%)	0	0/186 (0%)	0	2/135 (1.5%)	2
Diverticulitis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Endocarditis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Enterovirus Infection	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Epstein-Barr Virus Infection	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Gastroenteritis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Herpes Simplex	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Herpes Zoster	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Influenza	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Lower Respiratory Tract Infection	1/184 (0.5%)	1	1/186 (0.5%)	2	0/135 (0%)	0
Meningitis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Osteomyelitis	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Otitis Externa	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	2
Periorbital Cellulitis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pharyngitis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Pneumocystis Jiroveci Pneumonia	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pneumonia	4/184 (2.2%)	4	2/186 (1.1%)	2	2/135 (1.5%)	2
Pneumonia Influenzal	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pneumonia Legionella	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pneumonia Pneumococcal	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Postoperative Wound Infection	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Respiratory Tract Infection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Rhinovirus Infection	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Sepsis	3/184 (1.6%)	4	5/186 (2.7%)	5	2/135 (1.5%)	2
Sepsis Syndrome	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Septic Embolus	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Septic Shock	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Skin Infection	0/184 (0%)	0	3/186 (1.6%)	3	0/135 (0%)	0
Staphylococcal Abscess	1/184 (0.5%)	2	0/186 (0%)	0	0/135 (0%)	0
Staphylococcal Bacteraemia	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Staphylococcal Infection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Staphylococcal Sepsis	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Superinfection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Upper Respiratory Tract Infection	0/184 (0%)	0	2/186 (1.1%)	2	0/135 (0%)	0
Urinary Tract Infection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Urinary Tract Infection Bacterial	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Viral Infection	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Wound Infection	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Injury, poisoning and procedural complications
Fall	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Femur Fracture	0/184 (0%)	0	0/186 (0%)	0	2/135 (1.5%)	2
Infusion Related Reaction	3/184 (1.6%)	3	0/186 (0%)	0	4/135 (3%)	4
Laceration	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Lower Limb Fracture	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Pelvic Fracture	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Subdural Haematoma	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Subdural Haemorrhage	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Vascular Access Complication	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Investigations
Alanine Aminotransferase Increased	2/184 (1.1%)	3	0/186 (0%)	0	1/135 (0.7%)	1
Aspartate Aminotransferase Increased	2/184 (1.1%)	3	0/186 (0%)	0	1/135 (0.7%)	1
Blood Alkaline Phospatase Increased	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Blood Creatinine Increased	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Dehydration	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Gout	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Hypercalcaemia	3/184 (1.6%)	3	0/186 (0%)	0	0/135 (0%)	0
Hyperglycaemia	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Hypoalbuminaemia	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Hypokalaemia	0/184 (0%)	0	1/186 (0.5%)	2	0/135 (0%)	0
Hyponatraemia	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Metabolic Acidosis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/184 (1.1%)	2	1/186 (0.5%)	1	0/135 (0%)	0
Back Pain	1/184 (0.5%)	1	1/186 (0.5%)	1	0/135 (0%)	0
Monarthritis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Muscular Weakness	1/184 (0.5%)	2	0/186 (0%)	0	0/135 (0%)	0
Musculoskeletal Chest Pain	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Myalgia	0/184 (0%)	0	1/186 (0.5%)	1	1/135 (0.7%)	2
Myositis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Osteoarthritis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Polymyositis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Basal Cell Carcinoma	1/184 (0.5%)	1	0/186 (0%)	0	1/135 (0.7%)	1
Bladder Transitional Cell Carcinoma	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Bowen's Disease	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Colon Cancer	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Infected Neoplasm	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Malignant Melanoma	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Malignant Pleural Effusion	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Metastases to Lymph Nodes	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Mycosis Fungoides	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Ovarian Cancer	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Squamous Cell Carcinoma	0/184 (0%)	0	1/186 (0.5%)	3	1/135 (0.7%)	1
Nervous system disorders
Depressed Level of Consciousness	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Haemorrhage Intracranial	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Hepatic Encephalopathy	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Metabolic Encephalopathy	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Miller Fisher Syndrome	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Monoparesis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Motor Dysfunction	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Psychiatric disorders
Confusional State	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Depression	1/184 (0.5%)	1	0/186 (0%)	0	1/135 (0.7%)	1
Mental Status Changes	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Renal and urinary disorders
Haematuria	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Renal Failure	1/184 (0.5%)	2	0/186 (0%)	0	0/135 (0%)	0
Renal Failure Acute	2/184 (1.1%)	2	1/186 (0.5%)	1	0/135 (0%)	0
Renal Impairment	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Urinary Retention	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Reproductive system and breast disorders
Oedema Genital	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Bronchitis Chronic	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Chronic Obstructive Pulmonary Disease	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Dyspnoea Exertional	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Haemoptysis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Interstitial Lung Disease	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pleural Effusion	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pneumonitis	1/184 (0.5%)	1	0/186 (0%)	0	1/135 (0.7%)	1
Pulmonary Embolism	0/184 (0%)	0	5/186 (2.7%)	5	1/135 (0.7%)	1
Respiratory Failure	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis Exfoliative	1/184 (0.5%)	1	1/186 (0.5%)	1	1/135 (0.7%)	1
Drug Eruption	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Photosensitivity Reaction	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Pruritis	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Skin Disorder	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Urticaria	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Social circumstances
Social Stay Hospitalization	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Surgical and medical procedures
Cardiac Pacemaker Replacement	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Vascular disorders
Air Embolism	0/184 (0%)	0	1/186 (0.5%)	1	0/135 (0%)	0
Aortic Stenosis	0/184 (0%)	0	0/186 (0%)	0	1/135 (0.7%)	1
Embolism	2/184 (1.1%)	2	0/186 (0%)	0	0/135 (0%)	0
Peripheral Arterial Occlusive Disease	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Phlebitis	1/184 (0.5%)	1	0/186 (0%)	0	0/135 (0%)	0
Other (Not Including Serious) Adverse Events
	KW-0761		Vorinostat		Vorinostat Original Then Crossover to KW-0761
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	178/184 (96.7%)		182/186 (97.8%)		128/135 (94.8%)
Blood and lymphatic system disorders
Anaemia	20/184 (10.9%)	35	18/186 (9.7%)	20	9/135 (6.7%)	10
Neutropenia	0/184 (0%)	0	0/186 (0%)	0	7/135 (5.2%)	8
Thrombocytopenia	21/184 (11.4%)	34	56/186 (30.1%)	83	11/135 (8.1%)	48
Eye disorders
Dry Eye	7/184 (3.8%)	7	11/186 (5.9%)	11	0/135 (0%)	0
Vision Blurred	8/184 (4.3%)	9	12/186 (6.5%)	14	0/135 (0%)	0
Gastrointestinal disorders
Abdominal Pain	7/184 (3.8%)	8	21/186 (11.3%)	24	7/135 (5.2%)	7
Abdominal Pain Upper	1/184 (0.5%)	1	11/186 (5.9%)	12	0/135 (0%)	0
Constipation	23/184 (12.5%)	27	34/186 (18.3%)	37	15/135 (11.1%)	15
Diarrhoea	45/184 (24.5%)	62	114/186 (61.3%)	180	22/135 (16.3%)	33
Dry Mouth	4/184 (2.2%)	4	17/186 (9.1%)	17	0/135 (0%)	0
Dyspepsia	1/184 (0.5%)	1	11/186 (5.9%)	11	0/135 (0%)	0
Nausea	29/184 (15.8%)	38	78/186 (41.9%)	99	10/135 (7.4%)	13
Stomatitis	10/184 (5.4%)	16	2/186 (1.1%)	3	0/135 (0%)	0
Vomiting	12/184 (6.5%)	13	23/186 (12.4%)	33	0/135 (0%)	0
General disorders
Asthenia	10/184 (5.4%)	12	25/186 (13.4%)	32	11/135 (8.1%)	18
Chills	13/184 (7.1%)	17	14/186 (7.5%)	15	8/135 (5.9%)	8
Fatigue	44/184 (23.9%)	55	69/186 (37.1%)	75	14/135 (10.4%)	19
Oedema Peripheral	27/184 (14.7%)	32	26/186 (14%)	37	13/135 (9.6%)	16
Pyrexia	26/184 (14.1%)	28	11/186 (5.9%)	11	17/135 (12.6%)	25
Infections and infestations
Bronchitis	0/184 (0%)	0	0/186 (0%)	0	9/135 (6.7%)	12
Folliculitis	14/184 (7.6%)	19	4/186 (2.2%)	4	13/135 (9.6%)	18
Nasopharyngitis	13/184 (7.1%)	19	16/186 (8.6%)	23	9/135 (6.7%)	12
Oral Candidasis	10/184 (5.4%)	10	1/186 (0.5%)	1	0/135 (0%)	0
Skin Infection	17/184 (9.2%)	28	10/186 (5.4%)	15	0/135 (0%)	0
Upper Respiratory Tract Infection	20/184 (10.9%)	28	8/186 (4.3%)	9	12/135 (8.9%)	22
Urinary Tract Infection	13/184 (7.1%)	17	14/186 (7.5%)	20	7/135 (5.2%)	8
Injury, poisoning and procedural complications
Fall	0/184 (0%)	0	0/186 (0%)	0	8/135 (5.9%)	8
Infusion Related Reaction	59/184 (32.1%)	83	0/186 (0%)	0	47/135 (34.8%)	55
Investigations
Alanine Aminotransferase Increased	0/184 (0%)	0	0/186 (0%)	0	12/135 (8.9%)	13
Aspartate Aminotransferase Increased	7/184 (3.8%)	8	12/186 (6.5%)	19	13/135 (9.6%)	15
Blood Creatinine Increased	6/184 (3.3%)	9	52/186 (28%)	58	0/135 (0%)	0
Platelet Count Decreased	4/184 (2.2%)	6	19/186 (10.2%)	22	0/135 (0%)	0
Weight Decreased	11/184 (6%)	15	32/186 (17.2%)	35	9/135 (6.7%)	9
Weight Increased	15/184 (8.2%)	17	2/186 (1.1%)	2	0/135 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	14/184 (7.6%)	14	45/186 (24.2%)	49	0/135 (0%)	0
Hyperglycaemia	15/184 (8.2%)	29	13/186 (7%)	28	0/135 (0%)	0
Hypokalaemia	11/184 (6%)	15	11/186 (5.9%)	16	0/135 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	13/184 (7.1%)	14	11/186 (5.9%)	17	15/135 (11.1%)	17
Back Pain	17/184 (9.2%)	20	9/186 (4.8%)	10	10/135 (7.4%)	13
Muscle Spasms	10/184 (5.4%)	11	29/186 (15.6%)	49	0/135 (0%)	0
Muscular Weakness	0/184 (0%)	0	0/186 (0%)	0	7/135 (5.2%)	7
Myalgia	12/184 (6.5%)	14	8/186 (4.3%)	8	0/135 (0%)	0
Pain In Extremity	13/184 (7.1%)	17	10/186 (5.4%)	16	13/135 (9.6%)	13
Nervous system disorders
Dizziness	12/184 (6.5%)	13	19/186 (10.2%)	20	8/135 (5.9%)	11
Dysgeusia	8/184 (4.3%)	8	55/186 (29.6%)	59	0/135 (0%)	0
Headache	23/184 (12.5%)	35	27/186 (14.5%)	32	17/135 (12.6%)	32
Paraesthesia	5/184 (2.7%)	5	14/186 (7.5%)	16	8/135 (5.9%)	10
Psychiatric disorders
Depression	10/184 (5.4%)	10	6/186 (3.2%)	6	0/135 (0%)	0
Insomnia	16/184 (8.7%)	16	14/186 (7.5%)	14	0/135 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	18/184 (9.8%)	20	16/186 (8.6%)	19	9/135 (6.7%)	9
Dyspnoea	10/184 (5.4%)	14	7/186 (3.8%)	8	0/135 (0%)	0
Oropharyngeal Pain	11/184 (6%)	11	5/186 (2.7%)	7	7/135 (5.2%)	8
Skin and subcutaneous tissue disorders
Alopecia	13/184 (7.1%)	13	35/186 (18.8%)	35	9/135 (6.7%)	9
Drug Eruption	44/184 (23.9%)	77	1/186 (0.5%)	2	35/135 (25.9%)	54
Intertrigo	0/184 (0%)	0	0/186 (0%)	0	7/135 (5.2%)	12
Rash	0/184 (0%)	0	0/186 (0%)	0	11/135 (8.1%)	15
Vascular disorders
Hypertension	17/184 (9.2%)	38	25/186 (13.4%)	28	0/135 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.