Phase II Study of KW-0761 in Subjects With CCR4-positive Adult T-cell Leukemia-lymphoma

Study Overview
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Brief Summary
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To evaluate the efficacy, safety and pharmacokinetic profiles of KW-0761, the anti-CC chemokine receptor 4 (CCR4) antibody, when administered weekly for 8 weeks as an intravenous infusion at a dose of 1.0 mg/kg in relapsed subjects with CCR4-positive adult T-cell leukemia-lymphoma.

Official Title
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Phase II Clinical Study of KW-0761 in Patients With CCR4-Positive Adult T-cell Leukemia-Lymphoma

Conditions
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Adult T-cell Leukemia-lymphoma

Intervention / Treatment
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* Biological: KW-0761


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive for serum anti-HTLV-I antibody Acute-, lymphoma-, or chronic-type with poor prognostic factors specified in the past Positive for CCR4 Relapsed subject after the response (CR, CRu or PR) in the last previous chemotherapy Received at least one prior chemotherapy Subjects with an interval of four weeks or more between the last day of the previous treatment and the scheduled day of the first KW-0761 treatment PS of 0 to 2 Negative for HBs antigen and for HBV-DNA by a real-time PCR Exclusion Criteria: A history of transplantation such as hematopoietic stem cells Positive for HCV antibody or HIV antibody Active multiple cancers at the time of starting this clinical study Previous history of allergic reactions after receiving antibody products Requiring continuous systemic treatment with a steroid Requiring such radiotherapy after starting this clinical study Treated with any investigational drug other than KW-0761 within three months

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KW-0761<br> | Biological: KW-0761<br>* KW-0761 is administered weekly for 8 weeks as an intravenous infusion of 2 hours at a dose of 1.0 mg/kg.<br>* Other names: Mogamulizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Response rate defined as the proportion of responders relative to the total population and its exact 95% confidence interval were calculated for best overall response. The antitumor response criteria (Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) were created based on the criteria for non-Hodgkin's lymphoma and chronic lymphocytic leukemia provided in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as well as the criteria for non-Hodgkin's lymphoma by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG).Overall Response (OR)= CR + PR. | From date of first subject's consent to participate in the study until the date of last protocol-specified examination for last subject completed, assessed up to 14 months. | 
| Pharmacokinetics-Plasma KW-0761 Concentrations | Statistics of plasma KW-0761 concentrations were tabulated. Individual and mean (+standard deviation) plasma KW-0761 concentrations were plotted on a linear and a logarithmic scale against the time of blood sampling. The baseline and maximum time point at which Cmax and Ctrough were collected are 0 to 7 days post-dose. | 0 to 7 days post final dose | 
| Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days) | Statistics of plasma KW-0761 concentrations were tabulated. Individual and mean (+standard deviation) plasma KW-0761 concentrations were plotted on a linear and a logarithmic scale against the time of blood sampling. | 0 to 7 days post final dose | 
| Pharmacokinetics-Plasma KW-0761 Concentrations (t1/2) |  | 0 to 28 days post final dose and follow-up examinations (1 month and 3 months after the end of the post-dosing observation period). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The time from the date of first KW-0761 dosing to the date of progressive disease(PD) confirmation or death. The antitumor response criteria including PD were created based on the criteria for non-Hodgkin's lymphoma and chronic lymphocytic leukemia provided in the National Comprehensive Cancer Network(NCCN) Clinical Practice Guidelines in Oncology as well as the criteria for non-Hodgkin's lymphoma by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG). | Baseline to response | 
| Overall Survival (OS) | The time from the date of first KW-0761 dosing to the date of death. | Baseline to response |