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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01728805
Recruitment Status : Completed
First Posted : November 20, 2012
Results First Posted : April 11, 2019
Last Update Posted : May 19, 2021
Information provided by (Responsible Party):
Kyowa Kirin, Inc.

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.

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Study Type : Interventional  (Clinical Trial)
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 : November 2012
Actual Primary Completion Date : March 2017
Actual Study Completion Date : February 17, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Vorinostat

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

Active Comparator: Vorinostat
vorinostat 400 mg once daily
Drug: Vorinostat
Other Names:
  • 400 mg orally daily

Primary Outcome Measures :
  1. Progression Free Survival [ 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 ]

    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 [ 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 ]
    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 [ Time Frame: 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 [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01728805

Hide Hide 73 study locations
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United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Banner MD Anderson
Gilbert, Arizona, United States, 85234
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
UCLA Medical Center
Los Angeles, California, United States, 90095
Stanford Medical Center
Stanford, California, United States, 94305
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine - Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
The Winship Cancer Institute (Emory University)
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
United States, Louisiana
Tulane University Medical Center
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Medical Center, Department of Medicine, Section of Hem/Onc
Boston, Massachusetts, United States, 02118
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Universal Dermatology, PLLC
Fairport, New York, United States, 14450
Columbia Presbyterian
New York, New York, United States, 10037
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
University of Rochester School of Medicine
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States, 15208
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
M.D.Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53266
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Parkville Cancer Clinical Trials Unit
Melbourne, Victoria, Australia, 3000
Aarhus University Hospital
Aarhus, Denmark, 8000
CHU de Nantes
Nantes, France, 44093
Hôpital Saint Louis
Paris, France, 75010
CHU Bordeaux - Hopital Haut-Leveque
Pessac, France, 33604
Centre Hospitalier Lyon Sud
Pierre-Benite Cedex, France, 69495
University Medical Centre Mannheim
Mannheim, Germany, D-68167
University Hospital Muenster
Muenster, Germany, 48149
Institute of Hematology and Oncology Lorenzo e Ariosto Seràgnoli, University of Bologna
Bologna, Italy, 40138
Universita degli Studi di Torino
Turin, Italy, 10124
Nagoya City University Hospital
Nagoya-shi, Aichi, Japan, 467-8602
Fukushima Medical University Hospital
Fukushima-shi, Fukushima, Japan, 960-1295
Gunma University Hospital
Maebashi-shi, Gunma, Japan, 371-8511
Hiroshima University Hospital
Hiroshima-shi, Hiroshima, Japan, 734-8551
Asahikawa Medical University Hospital
Asahikawa, Hokkaido, Japan, 078-8510
Imamura Bun-in Hospital
Kagoshima-shi, Kagoshima, Japan, 890-0064
Yokohama City University Hospital
Yokohama-shi, Kanagawa, Japan, 236-0004
Kochi Medical School Hospital
Nankoku-shi, Kochi, Japan, 783-8505
Mie University Hospital
Tsu-shi, Mie, Japan, 514-8507
Tohoku University Hospital
Sendai-shi, Miyagi, Japan, 980-8574
Shinshu University Hospital
Matsumoto-shi, Nagano, Japan, 390-8621
Okayama University Hospital
Okayama-shi, Okayama, Japan, 700-8558
Kansai Medical University Hospital
Hirakata-shi, Osaka, Japan, 571-1191
Osaka University Hospital
Suita-shi, Osaka, Japan, 565-0871
Hamamatsu University Hospital
Hamamatsu-shi, Shizuoka, Japan, 431-3192
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan, 113-8655
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 104-0045
Tokyo Metropolitan Tama Medical Center
Fuchu-shi, Tokyo, Japan, 183-8524
Japanese Foundation for Cancer Research
Koto-ku, Tokyo, Japan, 135-8550
Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
Leiden, Netherlands, 2300RC
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
University Hospital Zurich
Zurich, Switzerland, 8091
United Kingdom
The Christie Hospital Foundation NHS Trust
Manchester, Greater Manchester, United Kingdom, M20 4BX
University Hospital Birmingham
Birmingham, United Kingdom, B15 2TH
Guys & St. Thomas NHS Trust
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Kyowa Kirin, Inc.
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Study Director: Dmitri O. Grebennik, MD Kyowa Kirin, Inc.
  Study Documents (Full-Text)

Documents provided by Kyowa Kirin, Inc.:
Study Protocol  [PDF] May 31, 2018
Statistical Analysis Plan  [PDF] November 22, 2016

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Kyowa Kirin, Inc. Identifier: NCT01728805    
Other Study ID Numbers: 0761-010
First Posted: November 20, 2012    Key Record Dates
Results First Posted: April 11, 2019
Last Update Posted: May 19, 2021
Last Verified: April 2021
Keywords provided by Kyowa Kirin, Inc.:
Cutaneous T-Cell Lymphoma (CTCL)
myocis fungoides (MF)
Sezary Syndrome (SS)
Additional relevant MeSH terms:
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Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action