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

Cutaneous T-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01728805
• Other study ID #: 0761-010
• Status: Completed
• Phase: Phase 3
• Start date: November 2012
• Est. completion date: February 17, 2021

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 372
• Est. completion date: February 17, 2021
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ß-HCG]) or lactating.

• History of allogeneic transplant.

Related Conditions & MeSH terms

• Cutaneous T-Cell Lymphoma
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral

Intervention

Biological:
• KW-0761
1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression

Drug:
• Vorinostat

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kyowa Kirin, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate	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.	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
Secondary	Quality of Life (QoL) Assessment - Skindex-29 Symptoms Scale Score	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.	Cycle 1, 3, and 5
Secondary	Pruritis Evaluation	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.	Cycle 1, 3, and 5