KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)

Tracking Information
First Submitted Date ICMJE	June 19, 2012
First Posted Date ICMJE	June 25, 2012
Results First Submitted Date	April 2, 2018
Results First Posted Date	June 15, 2018
Last Update Posted Date	June 15, 2018
Study Start Date ICMJE	June 2012
Actual Primary Completion Date	August 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 16, 2018)	Overall Response Rate [ Time Frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first ]; Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = > 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment. Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
Original Primary Outcome Measures ICMJE; (submitted: June 22, 2012)	Overall Response Rate [ Time Frame: every 8 weeks ]
Change History	Complete list of historical versions of study NCT01626664 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 16, 2018)	Progression Free Survival [ Time Frame: From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months ]Progression-free survival was defined as the time from the first date of treatment until the date that PD or death was first reported. Disease progression included PD in any compartment per ATL response criteria, clinical progression at the end of the randomized treatment, or disease progression reported during the follow-up period. The date of PD was the earliest date at which disease progression could be declared.; Overall Survival [ Time Frame: up to 36 months ]The estimates and summary statistics for OS were calculated based on Kaplan-Meier method, and the median OS was 4.9 months for subjects randomized to the mogamulizumab group versus 6.87 months for subjects randomized to the Investigator's Choice group.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Official Title ICMJE	Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
Brief Summary	The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL).
Detailed Description	CCR4 expression in ATL patients has been demonstrated to be very high and has been associated with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for subjects with relapsed or refractory ATL.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Adult T-cell Leukemia-Lymphoma
Intervention ICMJE	Biological: KW-0761 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression Other Names: mogamulizumab POTELIGEO®; Drug: Pralatrexate 30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression Other Name: Folotyn; Drug: gemcitabine plus oxaliplatin gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression Other Names: Gemzar Eloxatin GemOx; Drug: DHAP dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression Other Names: Decadron, Dexasone, Baycadron Platinol Depocyt, Ara-C
Study Arms	Experimental: KW-0761 anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) Intervention: Biological: KW-0761; Active Comparator: investigator's choice Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Interventions: Drug: Pralatrexate Drug: gemcitabine plus oxaliplatin Drug: DHAP
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 14, 2016)	71
Original Estimated Enrollment ICMJE; (submitted: June 22, 2012)	70
Actual Study Completion Date	February 2018
Actual Primary Completion Date	August 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Males and female subjects ≥ 18 years of age; Confirmed diagnosis of ATL (excluding smoldering subtype); Subjects must currently have evidence of disease in at least one of the following: Lymph nodes Extranodal masses Spleen or liver Skin Peripheral blood Bone marrow; Relapsed or refractory after at least one prior systemic therapy regimen for ATL;; Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 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, hepatic and renal function Exclusion Criteria: Smoldering subtype of ATL;; Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;; History of allogeneic transplant;; Autologous hematopoietic stem cell transplant within 90 days of study entry;; Untreated human immunodeficiency virus (HIV); Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;; Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are hepatitis B core antibody positive but PCR negative may be enrolled if placed on appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with KW-0761. Patients who are hepatitis B core antibody positive based on prior vaccination need not receive prophylaxis;; Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease;; Clinical evidence of central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture should be done to confirm;; Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;; Significant uncontrolled intercurrent illness; Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;; Known active autoimmune diseases will be excluded (For example; Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);; Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.; Prior treatment with KW-0761;; Initiation of treatment with systemic corticosteroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects (e.g., including pre-medication for infusion reaction, nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be off for 7 days before initiation of study treatment, unless specifically indicated for the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and replacement doses of systemic corticosteroids as needed);; Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to taper the use to lowest dose tolerable;; Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks of first study treatment;; Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, Brazil, France, Peru, United Kingdom, United States
Removed Location Countries	Romania
Administrative Information
NCT Number ICMJE	NCT01626664
Other Study ID Numbers ICMJE	PROTOCOL 0761-009
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Kyowa Kirin Pharmaceutical Development, Inc.
Study Sponsor ICMJE	Kyowa Kirin Pharmaceutical Development, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Michael Kurman, MD Kyowa Hakko Kirin Pharma, Inc.
PRS Account	Kyowa Kirin Pharmaceutical Development, Inc.
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP