Clinical trial NCT01728805: Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cutaneous T-Cell Lymphoma
Keywords: Cutaneous T-Cell Lymphoma (CTCL)
myocis fungoides (MF)
Sezary Syndrome (SS)
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2012-11-20
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 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:
measure: Overall Response Rate
timeFrame: 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
measure: Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score
timeFrame: Cycle 1, 3, and 5
measure: Pruritis Evaluation
timeFrame: Cycle 1, 3, and 5
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: The Winship Cancer Institute (Emory University)
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center, Department of Medicine, Section of Hem/Onc
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Fairport
country: United States
facility: Universal Dermatology, PLLC
state: New York
city: New York
country: United States
facility: Columbia Presbyterian
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester School of Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: M.D.Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: Parkville Cancer Clinical Trials Unit
state: Victoria
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pessac
country: France
facility: CHU Bordeaux - Hopital Haut-Leveque
city: Pierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Mannheim
country: Germany
facility: University Medical Centre Mannheim
city: Muenster
country: Germany
facility: University Hospital Muenster
city: Bologna
country: Italy
facility: Institute of Hematology and Oncology Lorenzo e Ariosto Seràgnoli, University of Bologna
city: Turin
country: Italy
facility: Universita degli Studi di Torino
city: Nagoya-shi
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Maebashi-shi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
state: Hokkaido
city: Kagoshima-shi
country: Japan
facility: Imamura Bun-in Hospital
state: Kagoshima
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Nankoku-shi
country: Japan
facility: Kochi Medical School Hospital
state: Kochi
city: Tsu-shi
country: Japan
facility: Mie University Hospital
state: Mie
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Matsumoto-shi
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Hamamatsu-shi
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fuchu-shi
country: Japan
facility: Tokyo Metropolitan Tama Medical Center
state: Tokyo
city: Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
state: Tokyo
city: Leiden
country: Netherlands
facility: Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Manchester
country: United Kingdom
facility: The Christie Hospital Foundation NHS Trust
state: Greater Manchester
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
city: London
country: United Kingdom
facility: Guys & St. Thomas NHS Trust
Study officials:
affiliation: Kyowa Kirin, Inc.
name: Dmitri O. Grebennik, MD
role: STUDY_DIRECTOR
References:
citation: 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.