Adult T-cell Leukemia-lymphoma
Conditions
Brief summary
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.
Interventions
BIOLOGICALKW-0761
KW-0761 is administered weekly for 8 weeks as an intravenous infusion of 2 hours at a dose of 1.0 mg/kg.
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Positive for serum anti-HTLV-I antibody 2. Acute-, lymphoma-, or chronic-type with poor prognostic factors specified in the past 3. Positive for CCR4 4. Relapsed subject after the response (CR, CRu or PR) in the last previous chemotherapy 5. Received at least one prior chemotherapy 6. 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 7. PS of 0 to 2 8. Negative for HBs antigen and for HBV-DNA by a real-time PCR
Exclusion criteria
1. A history of transplantation such as hematopoietic stem cells 2. Positive for HCV antibody or HIV antibody 3. Active multiple cancers at the time of starting this clinical study 4. Previous history of allergic reactions after receiving antibody products 5. Requiring continuous systemic treatment with a steroid 6. Requiring such radiotherapy after starting this clinical study 7. Treated with any investigational drug other than KW-0761 within three months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 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. | 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. |
| Pharmacokinetics-Plasma KW-0761 Concentrations | 0 to 7 days post final dose | 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. |
| Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days) | 0 to 7 days post final dose | 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline to response | The time from the date of first KW-0761 dosing to the date of death. |
| Progression Free Survival (PFS) | Baseline to response | 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). |
Countries
Japan
Participant flow
Recruitment details
Participants were enrolled from 1 June 2009 through 9 November 2010
Participants by arm
| Arm | Count |
|---|---|
| KW-0761 IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | aggravation of general condition | 14 |
Baseline characteristics
| Characteristic | KW-0761 |
|---|---|
| Age, Continuous | 64 years FULL_RANGE 7.5 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 6 / 27 |
Outcome results
Primary
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.
Time frame: 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.
Population: Of the 27 subjects enrolled, 26 were included in the efficacy analysis set, whereas 1 was excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KW-0761 | Overall Response Rate (ORR) | 50 percentage of participants with response |
Primary
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.
Time frame: 0 to 7 days post final dose
Population: Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KW-0761 | Pharmacokinetics-Plasma KW-0761 Concentrations | Cmax | 42943.2 ng/mL | Standard Deviation 14239.5 |
| KW-0761 | Pharmacokinetics-Plasma KW-0761 Concentrations | Ctrough | 33638.3 ng/mL | Standard Deviation 10572.2 |
Primary
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.
Time frame: 0 to 7 days post final dose
Population: Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KW-0761 | Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days) | 6297408 ng·h/mL | Standard Deviation 1812467 |
Primary
Pharmacokinetics-Plasma KW-0761 Concentrations (t1/2)
Time frame: 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).
Population: Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KW-0761 | Pharmacokinetics-Plasma KW-0761 Concentrations (t1/2) | 422 hours | Standard Deviation 147 |
Secondary
Overall Survival (OS)
The time from the date of first KW-0761 dosing to the date of death.
Time frame: Baseline to response
Population: Of the 27 subjects enrolled, 26 were included in the overall survival analysis set, whereas 1 was excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KW-0761 | Overall Survival (OS) | 176.5 days |
Secondary
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).
Time frame: Baseline to response
Population: Of the 27 subjects enrolled, 26 were included in the efficacy analysis set, whereas 1 was excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KW-0761 | Progression Free Survival (PFS) | 97 days |