Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL
- Registration Number
- NCT01728805
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 372
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KW-0761 KW-0761 anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) Vorinostat Vorinostat vorinostat 400 mg once daily
- Primary Outcome Measures
Name Time Method Progression Free Survival 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
Name Time Method 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 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.
Pruritis Evaluation 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.Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score 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.
Trial Locations
- Locations (73)
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh School of Medicine
🇺🇸Pittsburgh, Pennsylvania, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Guys & St. Thomas NHS Trust
🇬🇧London, United Kingdom
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Parkville Cancer Clinical Trials Unit
🇦🇺Melbourne, Victoria, Australia
CHU Bordeaux - Hopital Haut-Leveque
🇫🇷Pessac, France
Fukushima Medical University Hospital
🇯🇵Fukushima-shi, Fukushima, Japan
The Christie Hospital Foundation NHS Trust
🇬🇧Manchester, Greater Manchester, United Kingdom
Hiroshima University Hospital
🇯🇵Hiroshima-shi, Hiroshima, Japan
Imamura Bun-in Hospital
🇯🇵Kagoshima-shi, Kagoshima, Japan
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
University Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
M.D.Anderson Cancer Center
🇺🇸Houston, Texas, United States
Banner MD Anderson
🇺🇸Gilbert, Arizona, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Washington
🇺🇸Seattle, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
CHU de Nantes
🇫🇷Nantes, France
Hôpital Saint Louis
🇫🇷Paris, France
Asahikawa Medical University Hospital
🇯🇵Asahikawa, Hokkaido, Japan
Stanford Medical Center
🇺🇸Stanford, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
The Winship Cancer Institute (Emory University)
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Columbia Presbyterian
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Universal Dermatology, PLLC
🇺🇸Fairport, New York, United States
University of Rochester School of Medicine
🇺🇸Rochester, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Aarhus University Hospital
🇩🇰Aarhus, Denmark
University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite Cedex, France
Mie University Hospital
🇯🇵Tsu-shi, Mie, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi, Japan
Shinshu University Hospital
🇯🇵Matsumoto-shi, Nagano, Japan
Okayama University Hospital
🇯🇵Okayama-shi, Okayama, Japan
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University Medical Centre Mannheim
🇩🇪Mannheim, Germany
University Hospital Muenster
🇩🇪Muenster, Germany
Universita degli Studi di Torino
🇮🇹Turin, Italy
The University of Tokyo Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Japanese Foundation for Cancer Research
🇯🇵Koto-ku, Tokyo, Japan
Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
🇳🇱Leiden, Netherlands
Boston Medical Center, Department of Medicine, Section of Hem/Onc
🇺🇸Boston, Massachusetts, United States
Nagoya City University Hospital
🇯🇵Nagoya-shi, Aichi, Japan
Gunma University Hospital
🇯🇵Maebashi-shi, Gunma, Japan
Kochi Medical School Hospital
🇯🇵Nankoku-shi, Kochi, Japan
Hamamatsu University Hospital
🇯🇵Hamamatsu-shi, Shizuoka, Japan
University Hospital Zurich
🇨🇭Zurich, Switzerland
Institute of Hematology and Oncology Lorenzo e Ariosto Seràgnoli, University of Bologna
🇮🇹Bologna, Italy
Yokohama City University Hospital
🇯🇵Yokohama-shi, Kanagawa, Japan
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Kansai Medical University Hospital
🇯🇵Hirakata-shi, Osaka, Japan
Osaka University Hospital
🇯🇵Suita-shi, Osaka, Japan
Tokyo Metropolitan Tama Medical Center
🇯🇵Fuchu-shi, Tokyo, Japan
Yale University School of Medicine - Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Tulane University Medical Center
🇺🇸New Orleans, Louisiana, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States