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

NCT ID: NCT01728805

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 372 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2021-02-17

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.

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.

Conditions

Cutaneous T-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KW-0761

anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)

Group Type: EXPERIMENTAL

KW-0761

Intervention Type: BIOLOGICAL

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

Vorinostat

vorinostat 400 mg once daily

Group Type: ACTIVE_COMPARATOR

Vorinostat

Intervention Type: DRUG

Interventions

KW-0761

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

Intervention Type: BIOLOGICAL

Vorinostat

Intervention Type: DRUG

Other Intervention Names

mogamulizumab; POTELIGEO®; 400 mg orally daily; ZOLINZA®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Kirin, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dmitri O. Grebennik, MD

Role: STUDY_DIRECTOR

Kyowa Kirin, Inc.

Locations

University of Alabama - Birmingham

Birmingham, Alabama, United States

Banner MD Anderson

Gilbert, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

UCLA Medical Center

Los Angeles, California, United States

Stanford Medical Center

Stanford, California, United States

University of Colorado

Aurora, Colorado, United States

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

The Winship Cancer Institute (Emory University)

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Tulane University Medical Center

New Orleans, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

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

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Universal Dermatology, PLLC

Fairport, New York, United States

Columbia Presbyterian

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Rochester School of Medicine

Rochester, New York, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

M.D.Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

University of Washington

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Westmead Hospital

Westmead, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Parkville Cancer Clinical Trials Unit

Melbourne, Victoria, Australia

Aarhus University Hospital

Aarhus, , Denmark

CHU de Nantes

Nantes, , France

Hôpital Saint Louis

Paris, , France

CHU Bordeaux - Hopital Haut-Leveque

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

University Medical Centre Mannheim

Mannheim, , Germany

University Hospital Muenster

Münster, , Germany

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

Bologna, , Italy

Universita degli Studi di Torino

Turin, , Italy

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Fukushima Medical University Hospital

Fukushima, Fukushima, Japan

Gunma University Hospital

Maebashi, Gunma, Japan

Hiroshima University Hospital

Hiroshima, Hiroshima, Japan

Asahikawa Medical University Hospital

Asahikawa, Hokkaido, Japan

Imamura Bun-in Hospital

Kagoshima, Kagoshima-ken, Japan

Yokohama City University Hospital

Yokohama, Kanagawa, Japan

Kochi Medical School Hospital

Nankoku-shi, Kochi, Japan

Mie University Hospital

Tsu, Mie-ken, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Shinshu University Hospital

Matsumoto-shi, Nagano, Japan

Okayama University Hospital

Okayama, Okayama-ken, Japan

Kansai Medical University Hospital

Hirakata-shi, Osaka, Japan

Osaka University Hospital

Suita-shi, Osaka, Japan

Hamamatsu University Hospital

Hamamatsu, Shizuoka, Japan

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Tokyo Metropolitan Tama Medical Center

Fuchu-shi, Tokyo, Japan

Japanese Foundation for Cancer Research

Koto-ku, Tokyo, Japan

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

Leiden, , Netherlands

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

University Hospital Zurich

Zurich, , Switzerland

The Christie Hospital Foundation NHS Trust

Manchester, Greater Manchester, United Kingdom

University Hospital Birmingham

Birmingham, , United Kingdom

Guys & St. Thomas NHS Trust

London, , United Kingdom

Countries

United States; Australia; Denmark; France; Germany; Italy; Japan; Netherlands; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39315857 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30100375 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

0761-010

Identifier Type: -

Identifier Source: org_study_id