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

NCT01728805 | Completed Phase 3 Results DMC

• 1 other identifier: 0761-010
• Study Type: interventional
• Target: 372
• Locations: 11 countries
• Sites: 73

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.

Conditions

Cutaneous T-Cell Lymphoma

Keywords

Cutaneous T-Cell Lymphoma (CTCL); myocis fungoides (MF); Sezary Syndrome (SS)

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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

  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

Secondary Outcomes (3)

• 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

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

  Cycle 1, 3, and 5

• Pruritis Evaluation

  Cycle 1, 3, and 5

Study Arms (2)

KW-0761

EXPERIMENTAL

anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)

Biological: KW-0761

Vorinostat

ACTIVE COMPARATOR

vorinostat 400 mg once daily

Drug: Vorinostat

Interventions

KW-0761 BIOLOGICAL

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

Also known as: mogamulizumab, POTELIGEO®

KW-0761

Vorinostat DRUG

Also known as: 400 mg orally daily, ZOLINZA®

Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (73)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Banner MD Anderson

Gilbert, Arizona, 85234, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford Medical Center

Stanford, California, 94305, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The Winship Cancer Institute (Emory University)

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center, Department of Medicine, Section of Hem/Onc

Boston, Massachusetts, 02118, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Universal Dermatology, PLLC

Fairport, New York, 14450, United States

Location

Columbia Presbyterian

New York, New York, 10037, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester School of Medicine

Rochester, New York, 14642, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15208, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

M.D.Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53266, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Parkville Cancer Clinical Trials Unit

Melbourne, Victoria, 3000, Australia

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

CHU de Nantes

Nantes, 44093, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

CHU Bordeaux - Hopital Haut-Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

University Medical Centre Mannheim

Mannheim, D-68167, Germany

Location

University Hospital Muenster

Münster, 48149, Germany

Location

Institute of Hematology and Oncology Lorenzo e Ariosto Seràgnoli, University of Bologna

Bologna, 40138, Italy

Location

Universita degli Studi di Torino

Turin, 10124, Italy

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Fukushima Medical University Hospital

Fukushima, Fukushima, 960-1295, Japan

Location

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

Location

Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551, Japan

Location

Asahikawa Medical University Hospital

Asahikawa, Hokkaido, 078-8510, Japan

Location

Imamura Bun-in Hospital

Kagoshima, Kagoshima-ken, 890-0064, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

Kochi Medical School Hospital

Nankoku-shi, Kochi, 783-8505, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Shinshu University Hospital

Matsumoto-shi, Nagano, 390-8621, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Kansai Medical University Hospital

Hirakata-shi, Osaka, 571-1191, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Hamamatsu University Hospital

Hamamatsu, Shizuoka, 431-3192, Japan

Location

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Tokyo Metropolitan Tama Medical Center

Fuchu-shi, Tokyo, 183-8524, Japan

Location

Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)

Leiden, 2300RC, Netherlands

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

The Christie Hospital Foundation NHS Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

University Hospital Birmingham

Birmingham, B15 2TH, United Kingdom

Location

Guys & St. Thomas NHS Trust

London, SE1 7EH, United Kingdom

Location

Related Publications (2)

• Ortiz Romero PL, Kim YH, Molloy K, Quaglino P, Scarisbrick J, Thornton S, Sandilands K, Dent JE, Nixon A, Williams A, Shinohara MM. Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sezary syndrome. J Eur Acad Dermatol Venereol. 2025 Apr;39(4):833-845. doi: 10.1111/jdv.20357. Epub 2024 Sep 24.

  PMID: 39315857 DERIVED

• 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.

  PMID: 30100375 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Sezary Syndrome

Interventions

mogamulizumab; Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Fiona Herr, Associate Director, Medical Communications
• Organization: Kyowa Kirin Inc

medinfo-US@kyowakirin.com

1 (908) 234-1096

Study Officials

• Dmitri O. Grebennik, MD

  Kyowa Kirin, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: November 20, 2012
• Study Start: November 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: February 17, 2021
• Last Updated: April 25, 2024
• Results First Posted: April 11, 2019

Record last verified: 2024-04

Locations

DK (1); AU (4); IT (2); ES (2); CH (1); JP (19); GB (3); NL (1); DE (2); FR (4); US (34)