Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Sezary Syndrome

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mogamulizumab

Vorinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)

1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression

KW-0761

Dmitri O. Grebennik, MD

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

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 of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL

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

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

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.

* 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.

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.

Kyowa Kirin, Inc.

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.

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

Subjects who were randomized to vorinostat could be crossed over to receive mogamulizumab upon disease progression and with permission from the Medical Monitor.

Vorinostat Original Then Crossover to KW-0761

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race/Ethnicity

Race/Ethnicity, Customized

Netherlands

United States

Japan

Denmark

Italy

United Kingdom

France

Australia

Switzerland

Germany

Spain

Region of Enrollment

Fiona Herr, Associate Director, Medical Communications

Rate (%) of Being Alive w/o Progression at 6 mos.

Rate (%) of Being Alive w/o Progression at 12 mos.

Rate (%) of Being Alive w/o Progression at 18 mos.

Rate (%) of Being Alive w/o Progression at 24 mos.

Rate (%) of Being Alive w/o Progression at 30 mos.

Progression Free Survival

All Subjects ORR (confirmed CR + PR)

Disease Type = MF ORR (confirmed CR + PR)

Disease Type = SS ORR (confirmed CR + PR)

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

Overall Response Rate

Skindex-29 Across 6-month Assessment

FACT-G Across 6-month Assessment

EQ-5D-3L Across 6-month Assessment

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

Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score

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

Pruritis Evaluation

Randomization Period

Crossover Period

Spots Global Cancer Trial Database for myocis fungoides (mf)