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

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ClinicalTrials.gov Identifier: NCT01728805

Recruitment Status : Completed

First Posted : November 20, 2012

Results First Posted : April 11, 2019

Last Update Posted : April 25, 2024

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Sponsor:

Information provided by (Responsible Party):

Kyowa Kirin Co., Ltd. ( Kyowa Kirin, Inc. )

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Cutaneous T-Cell Lymphoma
Interventions	Biological: KW-0761 Drug: Vorinostat
Enrollment	372

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	KW-0761	Vorinostat	Vorinostat Original Then Crossover to KW-0761
Arm/Group Description	anti-CCR4 monoclonal antibody KW-07...	vorinostat 400 mg once daily ...	Subjects who were randomized to vor...
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: Crossover 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-07...	vorinostat 400 mg once daily ...	Total of all reporting groups
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 Number of Baseline Participants		186	186	372
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	186 participants	186 participants	372 participants
	<=18 years	0 0.0%	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, Continuous Mean (Full Range) Unit of measure: Years
	Number Analyzed	186 participants	186 participants	372 participants
		62.8 (25 to 101)	63.3 (25 to 89)	63.0 (25 to 101)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	186 participants	186 participants	372 participants
	Female	77 41.4%	79 42.5%	156 41.9%
	Male	109 58.6%	107 57.5%	216 58.1%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race/Ethnicity	Number Analyzed	186 participants	186 participants	372 participants
	White	125 67.2%	135 72.6%	260 69.9%
	Other	37 19.9%	26 14.0%	63 16.9%
	Not Reported	24 12.9%	25 13.4%	49 13.2%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	186 participants	186 participants	372 participants
Netherlands		0	2	2
United States		98	103	201
Japan		9	6	15
Denmark		1	2	3
Italy		14	12	26
United Kingdom		16	14	30
France		23	24	47
Australia		9	7	16
Switzerland		2	2	4
Germany		5	6	11
Spain		9	8	17

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival
Description	Progression was defined as follows, based on Olsen (2011): ...
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-07...	vorinostat 400 mg once daily ...
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
Overall Number of Participants Analyzed	186	186
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of subjects
Rate (%) of Being Alive w/o Progression at 6 mos.	55.3 (47.1 to 62.6)	28.8 (21.6 to 36.3)
Rate (%) of Being Alive w/o Progression at 12 mos.	38.3 (30.2 to 46.4)	15.3 (9.5 to 22.3)
Rate (%) of Being Alive w/o Progression at 18 mos.	28.0 (19.8 to 36.8)	7.2 (2.7 to 14.5)
Rate (%) of Being Alive w/o Progression at 24 mos.	14.1 (6.4 to 24.8)	7.2 (2.7 to 14.5)
Rate (%) of Being Alive w/o Progression at 30 mos.	4.7 (0.5 to 17.7)	7.2 (2.7 to 14.5)

2.Secondary Outcome


Title	Overall Response Rate
Description	The ORR was defined as the count of subjects who had a confirmed CR or...
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-07...	vorinostat 400 mg once daily ...
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
Overall Number of Participants Analyzed		186	186
Measure Type: Count of Participants Unit of Measure: Participants
All Subjects ORR (confirmed CR + PR)	Number Analyzed	186 participants	186 participants
All Subjects ORR (confirmed CR + PR)		52 28.0%	9 4.8%
Disease Type = MF ORR (confirmed CR + PR)	Number Analyzed	105 participants	99 participants
Disease Type = MF ORR (confirmed CR + PR)		22 21.0%	7 7.1%
Disease Type = SS ORR (confirmed CR + PR)	Number Analyzed	81 participants	87 participants
Disease Type = SS ORR (confirmed CR + PR)		30 37.0%	2 2.3%

3.Secondary Outcome


Title	Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score
Description	...
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-07...	vorinostat 400 mg once daily ...
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
Overall Number of Participants Analyzed		186	186
Least Squares Mean (95% Confidence Interval) Unit of Measure: score on a scale
Skindex-29 Across 6-month Assessment	Number Analyzed	162 participants	171 participants
Skindex-29 Across 6-month Assessment		-12.6 (-15.94 to -9.29)	-6.0 (-9.39 to -2.52)
FACT-G Across 6-month Assessment	Number Analyzed	167 participants	177 participants
FACT-G Across 6-month Assessment		4.6 (2.14 to 7.04)	-2.3 (-4.84 to 0.21)
EQ-5D-3L Across 6-month Assessment	Number Analyzed	169 participants	174 participants
EQ-5D-3L Across 6-month Assessment		0.06 (0.028 to 0.085)	0.02 (-0.008 to 0.052)

4.Secondary Outcome


Title	Pruritis Evaluation
Description	The Itchy QoL is a validated pruritus specific quality of life instrum...
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-07...	vorinostat 400 mg once daily ...
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
Overall Number of Participants Analyzed	166	175
Least Squares Mean (95% Confidence Interval) Unit of Measure: score on a scale
	-0.5 (-0.66 to -0.39)	-0.4 (-0.52 to -0.24)

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-07...		vorinostat 400 mg once daily ...		Subjects who were randomized to vor...
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 (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	40/184 (21.74%)		47/186 (25.27%)		32/135 (23.70%)
Serious Adverse Events 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 (37.50%)		46/186 (24.73%)		40/135 (29.63%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Anaemia Haemolytic Autoimmune ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Febrile Neutropenia ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Haemolytic Anaemia ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Neutropenia ^† 1	0/184 (0.00%)	0	2/186 (1.08%)	2	0/135 (0.00%)	0
Thrombocytopenia ^† 1	0/184 (0.00%)	0	3/186 (1.61%)	4	0/135 (0.00%)	0
Cardiac disorders
Acute Myocardial Infarction ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	1/135 (0.74%)	1
Angina Pectoris ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Angina Unstable ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Atrial Fibrillation ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Cardiac Failure ^† 1	1/184 (0.54%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Left Ventricular Hypertrophy ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Myocarditis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Supraventricular Tachycardia ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Ear and labyrinth disorders
Ear Pain ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Eye disorders
Lens Dislocation ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Retinal Vein Occlusion ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Abdominal Pain Upper ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Anal Fistula ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Colitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Constipation ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Diarrhoea ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	1/135 (0.74%)	1
Gastric Haemorrhage ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Gastrointestinal Haemorrhage ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Ileitis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Inguinal Hernia ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Intestinal Obstruction ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Large Intestinal Ulcer Haemorrhage ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Lip Swelling ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Nausea ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Stomatitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	3
Vomiting ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
General disorders
Asthenia ^† 1	0/184 (0.00%)	0	2/186 (1.08%)	2	1/135 (0.74%)	1
Chest Discomfort ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Chest Pain ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	2/135 (1.48%)	2
Death ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Device Failure ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Disease Progression ^† 1	4/184 (2.17%)	4	1/186 (0.54%)	1	0/135 (0.00%)	0
Facial Pain ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Fatigue ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
General Physical Health Deterioration ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	2	0/135 (0.00%)	0
Hypothermia ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Localised Oedema ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Oedema ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Oedema Peripheral ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	2/135 (1.48%)	3
Pyrexia ^† 1	8/184 (4.35%)	9	1/186 (0.54%)	1	2/135 (1.48%)	5
Hepatobiliary disorders
Autoimmune Hepatitis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Cholangitis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Cholecystitis Acute ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Hepatic Failure ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Hepatitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Hepatitis Acute ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	1/135 (0.74%)	1
Hepatocellular Injury ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Immune system disorders
Contrast Media Allergy ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Drug Hypersensitivity ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Hypersensitivity ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Infections and infestations
Abscess Limb ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Appendicitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Arthritis Bacterial ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Atypical Pneumonia ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Bacteraemia ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Bronchitis ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Bronchopneumonia ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Cellulitis ^† 1	5/184 (2.72%)	5	6/186 (3.23%)	6	3/135 (2.22%)	3
Cytomegalovirus Infection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Device Related Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	2/135 (1.48%)	2
Diverticulitis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Endocarditis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Enterovirus Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Epstein-Barr Virus Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Gastroenteritis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Herpes Simplex ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Herpes Zoster ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Influenza ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Lower Respiratory Tract Infection ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	2	0/135 (0.00%)	0
Meningitis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Osteomyelitis ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Otitis Externa ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	2
Periorbital Cellulitis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pharyngitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Pneumocystis Jiroveci Pneumonia ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pneumonia ^† 1	4/184 (2.17%)	4	2/186 (1.08%)	2	2/135 (1.48%)	2
Pneumonia Influenzal ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pneumonia Legionella ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pneumonia Pneumococcal ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Postoperative Wound Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Respiratory Tract Infection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Rhinovirus Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Sepsis ^† 1	3/184 (1.63%)	4	5/186 (2.69%)	5	2/135 (1.48%)	2
Sepsis Syndrome ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Septic Embolus ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Septic Shock ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Skin Infection ^† 1	0/184 (0.00%)	0	3/186 (1.61%)	3	0/135 (0.00%)	0
Staphylococcal Abscess ^† 1	1/184 (0.54%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Staphylococcal Bacteraemia ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Staphylococcal Infection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Staphylococcal Sepsis ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Superinfection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Upper Respiratory Tract Infection ^† 1	0/184 (0.00%)	0	2/186 (1.08%)	2	0/135 (0.00%)	0
Urinary Tract Infection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Urinary Tract Infection Bacterial ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Viral Infection ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Wound Infection ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Injury, poisoning and procedural complications
Fall ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Femur Fracture ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	2/135 (1.48%)	2
Infusion Related Reaction ^† 1	3/184 (1.63%)	3	0/186 (0.00%)	0	4/135 (2.96%)	4
Laceration ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Lower Limb Fracture ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Pelvic Fracture ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Subdural Haematoma ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Subdural Haemorrhage ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Vascular Access Complication ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Investigations
Alanine Aminotransferase Increased ^† 1	2/184 (1.09%)	3	0/186 (0.00%)	0	1/135 (0.74%)	1
Aspartate Aminotransferase Increased ^† 1	2/184 (1.09%)	3	0/186 (0.00%)	0	1/135 (0.74%)	1
Blood Alkaline Phospatase Increased ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Blood Creatinine Increased ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Metabolism and nutrition disorders
Decreased Appetite ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Dehydration ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Gout ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Hypercalcaemia ^† 1	3/184 (1.63%)	3	0/186 (0.00%)	0	0/135 (0.00%)	0
Hyperglycaemia ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Hypoalbuminaemia ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Hypokalaemia ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	2	0/135 (0.00%)	0
Hyponatraemia ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Metabolic Acidosis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/184 (1.09%)	2	1/186 (0.54%)	1	0/135 (0.00%)	0
Back Pain ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	0/135 (0.00%)	0
Monarthritis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Muscular Weakness ^† 1	1/184 (0.54%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Musculoskeletal Chest Pain ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Myalgia ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	1/135 (0.74%)	2
Myositis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Osteoarthritis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Polymyositis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Basal Cell Carcinoma ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	1/135 (0.74%)	1
Bladder Transitional Cell Carcinoma ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Bowen's Disease ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Colon Cancer ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Infected Neoplasm ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Malignant Melanoma ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Malignant Pleural Effusion ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Metastases to Lymph Nodes ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Mycosis Fungoides ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Ovarian Cancer ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Squamous Cell Carcinoma ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	3	1/135 (0.74%)	1
Nervous system disorders
Depressed Level of Consciousness ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Haemorrhage Intracranial ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Hepatic Encephalopathy ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Metabolic Encephalopathy ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Miller Fisher Syndrome ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Monoparesis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Motor Dysfunction ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Psychiatric disorders
Confusional State ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Depression ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	1/135 (0.74%)	1
Mental Status Changes ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Renal and urinary disorders
Haematuria ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Renal Failure ^† 1	1/184 (0.54%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Renal Failure Acute ^† 1	2/184 (1.09%)	2	1/186 (0.54%)	1	0/135 (0.00%)	0
Renal Impairment ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Urinary Retention ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Reproductive system and breast disorders
Oedema Genital ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Bronchitis Chronic ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Chronic Obstructive Pulmonary Disease ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Dyspnoea Exertional ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Haemoptysis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Interstitial Lung Disease ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pleural Effusion ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pneumonitis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	1/135 (0.74%)	1
Pulmonary Embolism ^† 1	0/184 (0.00%)	0	5/186 (2.69%)	5	1/135 (0.74%)	1
Respiratory Failure ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis Exfoliative ^† 1	1/184 (0.54%)	1	1/186 (0.54%)	1	1/135 (0.74%)	1
Drug Eruption ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Photosensitivity Reaction ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Pruritis ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Skin Disorder ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Urticaria ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Social circumstances
Social Stay Hospitalization ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Surgical and medical procedures
Cardiac Pacemaker Replacement ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Vascular disorders
Air Embolism ^† 1	0/184 (0.00%)	0	1/186 (0.54%)	1	0/135 (0.00%)	0
Aortic Stenosis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	1/135 (0.74%)	1
Embolism ^† 1	2/184 (1.09%)	2	0/186 (0.00%)	0	0/135 (0.00%)	0
Peripheral Arterial Occlusive Disease ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
Phlebitis ^† 1	1/184 (0.54%)	1	0/186 (0.00%)	0	0/135 (0.00%)	0
1 Term from vocabulary, MedDRA (20.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (96.74%)		182/186 (97.85%)		128/135 (94.81%)
Blood and lymphatic system disorders
Anaemia ^† 1	20/184 (10.87%)	35	18/186 (9.68%)	20	9/135 (6.67%)	10
Neutropenia ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	7/135 (5.19%)	8
Thrombocytopenia ^† 1	21/184 (11.41%)	34	56/186 (30.11%)	83	11/135 (8.15%)	48
Eye disorders
Dry Eye ^† 1	7/184 (3.80%)	7	11/186 (5.91%)	11	0/135 (0.00%)	0
Vision Blurred ^† 1	8/184 (4.35%)	9	12/186 (6.45%)	14	0/135 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain ^† 1	7/184 (3.80%)	8	21/186 (11.29%)	24	7/135 (5.19%)	7
Abdominal Pain Upper ^† 1	1/184 (0.54%)	1	11/186 (5.91%)	12	0/135 (0.00%)	0
Constipation ^† 1	23/184 (12.50%)	27	34/186 (18.28%)	37	15/135 (11.11%)	15
Diarrhoea ^† 1	45/184 (24.46%)	62	114/186 (61.29%)	180	22/135 (16.30%)	33
Dry Mouth ^† 1	4/184 (2.17%)	4	17/186 (9.14%)	17	0/135 (0.00%)	0
Dyspepsia ^† 1	1/184 (0.54%)	1	11/186 (5.91%)	11	0/135 (0.00%)	0
Nausea ^† 1	29/184 (15.76%)	38	78/186 (41.94%)	99	10/135 (7.41%)	13
Stomatitis ^† 1	10/184 (5.43%)	16	2/186 (1.08%)	3	0/135 (0.00%)	0
Vomiting ^† 1	12/184 (6.52%)	13	23/186 (12.37%)	33	0/135 (0.00%)	0
General disorders
Asthenia ^† 1	10/184 (5.43%)	12	25/186 (13.44%)	32	11/135 (8.15%)	18
Chills ^† 1	13/184 (7.07%)	17	14/186 (7.53%)	15	8/135 (5.93%)	8
Fatigue ^† 1	44/184 (23.91%)	55	69/186 (37.10%)	75	14/135 (10.37%)	19
Oedema Peripheral ^† 1	27/184 (14.67%)	32	26/186 (13.98%)	37	13/135 (9.63%)	16
Pyrexia ^† 1	26/184 (14.13%)	28	11/186 (5.91%)	11	17/135 (12.59%)	25
Infections and infestations
Bronchitis ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	9/135 (6.67%)	12
Folliculitis ^† 1	14/184 (7.61%)	19	4/186 (2.15%)	4	13/135 (9.63%)	18
Nasopharyngitis ^† 1	13/184 (7.07%)	19	16/186 (8.60%)	23	9/135 (6.67%)	12
Oral Candidasis ^† 1	10/184 (5.43%)	10	1/186 (0.54%)	1	0/135 (0.00%)	0
Skin Infection ^† 1	17/184 (9.24%)	28	10/186 (5.38%)	15	0/135 (0.00%)	0
Upper Respiratory Tract Infection ^† 1	20/184 (10.87%)	28	8/186 (4.30%)	9	12/135 (8.89%)	22
Urinary Tract Infection ^† 1	13/184 (7.07%)	17	14/186 (7.53%)	20	7/135 (5.19%)	8
Injury, poisoning and procedural complications
Fall ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	8/135 (5.93%)	8
Infusion Related Reaction ^† 1	59/184 (32.07%)	83	0/186 (0.00%)	0	47/135 (34.81%)	55
Investigations
Alanine Aminotransferase Increased ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	12/135 (8.89%)	13
Aspartate Aminotransferase Increased ^† 1	7/184 (3.80%)	8	12/186 (6.45%)	19	13/135 (9.63%)	15
Blood Creatinine Increased ^† 1	6/184 (3.26%)	9	52/186 (27.96%)	58	0/135 (0.00%)	0
Platelet Count Decreased ^† 1	4/184 (2.17%)	6	19/186 (10.22%)	22	0/135 (0.00%)	0
Weight Decreased ^† 1	11/184 (5.98%)	15	32/186 (17.20%)	35	9/135 (6.67%)	9
Weight Increased ^† 1	15/184 (8.15%)	17	2/186 (1.08%)	2	0/135 (0.00%)	0
Metabolism and nutrition disorders
Decreased Appetite ^† 1	14/184 (7.61%)	14	45/186 (24.19%)	49	0/135 (0.00%)	0
Hyperglycaemia ^† 1	15/184 (8.15%)	29	13/186 (6.99%)	28	0/135 (0.00%)	0
Hypokalaemia ^† 1	11/184 (5.98%)	15	11/186 (5.91%)	16	0/135 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	13/184 (7.07%)	14	11/186 (5.91%)	17	15/135 (11.11%)	17
Back Pain ^† 1	17/184 (9.24%)	20	9/186 (4.84%)	10	10/135 (7.41%)	13
Muscle Spasms ^† 1	10/184 (5.43%)	11	29/186 (15.59%)	49	0/135 (0.00%)	0
Muscular Weakness ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	7/135 (5.19%)	7
Myalgia ^† 1	12/184 (6.52%)	14	8/186 (4.30%)	8	0/135 (0.00%)	0
Pain In Extremity ^† 1	13/184 (7.07%)	17	10/186 (5.38%)	16	13/135 (9.63%)	13
Nervous system disorders
Dizziness ^† 1	12/184 (6.52%)	13	19/186 (10.22%)	20	8/135 (5.93%)	11
Dysgeusia ^† 1	8/184 (4.35%)	8	55/186 (29.57%)	59	0/135 (0.00%)	0
Headache ^† 1	23/184 (12.50%)	35	27/186 (14.52%)	32	17/135 (12.59%)	32
Paraesthesia ^† 1	5/184 (2.72%)	5	14/186 (7.53%)	16	8/135 (5.93%)	10
Psychiatric disorders
Depression ^† 1	10/184 (5.43%)	10	6/186 (3.23%)	6	0/135 (0.00%)	0
Insomnia ^† 1	16/184 (8.70%)	16	14/186 (7.53%)	14	0/135 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	18/184 (9.78%)	20	16/186 (8.60%)	19	9/135 (6.67%)	9
Dyspnoea ^† 1	10/184 (5.43%)	14	7/186 (3.76%)	8	0/135 (0.00%)	0
Oropharyngeal Pain ^† 1	11/184 (5.98%)	11	5/186 (2.69%)	7	7/135 (5.19%)	8
Skin and subcutaneous tissue disorders
Alopecia ^† 1	13/184 (7.07%)	13	35/186 (18.82%)	35	9/135 (6.67%)	9
Drug Eruption ^† 1	44/184 (23.91%)	77	1/186 (0.54%)	2	35/135 (25.93%)	54
Intertrigo ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	7/135 (5.19%)	12
Rash ^† 1	0/184 (0.00%)	0	0/186 (0.00%)	0	11/135 (8.15%)	15
Vascular disorders
Hypertension ^† 1	17/184 (9.24%)	38	25/186 (13.44%)	28	0/135 (0.00%)	0
1 Term from vocabulary, MedDRA (20.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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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.

Results Point of Contact

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Name/Title:	Fiona Herr, Associate Director, Medical Communications
Organization:	Kyowa Kirin Inc
Phone:	1 (908) 234-1096
EMail:	medinfo-US@kyowakirin.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018 Sep;19(9):1192-1204. doi: 10.1016/S1470-2045(18)30379-6. Epub 2018 Aug 9. Erratum In: Lancet Oncol. 2018 Nov;19(11):e581.

Layout table for additonal information

Responsible Party:	Kyowa Kirin Co., Ltd. ( Kyowa Kirin, Inc. )
ClinicalTrials.gov Identifier:	NCT01728805
Other Study ID Numbers:	0761-010
First Submitted:	October 25, 2012
First Posted:	November 20, 2012
Results First Submitted:	October 11, 2018
Results First Posted:	April 11, 2019
Last Update Posted:	April 25, 2024

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