Trial Outcomes & Findings for Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL (NCT NCT00355472)
NCT ID: NCT00355472
Last Updated: 2012-10-18
Results Overview
Subjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
28 days
Results posted on
2012-10-18
Participant Flow
Participants were enrolled from 6 February 2007 through 22 October 2008
Participant milestones
| Measure |
KW-0761
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CC chemokine 4 receptor (CCR4) positive Adult T-Cell Leukemia-Lymphoma (ATL) or CCR4 positive Peripheral T-Cell Lymphoma (PTCL)
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
KW-0761
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CC chemokine 4 receptor (CCR4) positive Adult T-Cell Leukemia-Lymphoma (ATL) or CCR4 positive Peripheral T-Cell Lymphoma (PTCL)
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL
Baseline characteristics by cohort
| Measure |
KW-0761
n=16 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
|---|---|
|
Age Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Diagnosis
ATL
|
13 participants
n=5 Participants
|
|
Diagnosis
PTCL
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 daysSubjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.
Outcome measures
| Measure |
KW-0761
n=16 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Incidence of Dose-Limiting Toxicities (DLTs)
|
1 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 28 daysThe dose level at which Dose-Limiting Toxicity (DLT) was recognized was to be regarded as Maximum Tolerated Dose (MTD), and the dose level below MTD by one level was to be regarded as the recommended dose level (when MTD was not reached, 1.0 mg/kg was to be regarded as the recommended dose level) and 3 more subjects were to be newly added to the recommended dose level.
Outcome measures
| Measure |
KW-0761
n=16 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
1.0 mg/kg
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 0-7 days post final dosePlasma KW-0761 concentrations were to be summarized in tabular form with the descriptive statistics on a dose-by-dose basis. Individual and mean (+ standard deviation) plasma KW-0761 concentrations on an actual or logarithmic scale were to be plotted against the time of blood sampling.
Outcome measures
| Measure |
KW-0761
n=3 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
n=4 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Pharmacokinetics-Plasma KW-0761 Concentrations
Cmax
|
350.0 ng/mL
Standard Deviation 47.8
|
2806.7 ng/mL
Standard Deviation 1664.5
|
15181.2 ng/mL
Standard Deviation 872.0
|
40428.4 ng/mL
Standard Deviation 5350.8
|
|
Pharmacokinetics-Plasma KW-0761 Concentrations
Ctrough
|
158.2 ng/mL
Standard Deviation 7.4
|
1515.2 ng/mL
Standard Deviation 1873.4
|
6824.7 ng/mL
Standard Deviation 872.9
|
19516.8 ng/mL
Standard Deviation 4264.7
|
PRIMARY outcome
Timeframe: 0-7 days post final dosePopulation: AUC0-7 days
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
Outcome measures
| Measure |
KW-0761
n=3 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
n=4 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days)
|
36586 ng·h/mL
Standard Deviation 2987
|
327609 ng·h/mL
Standard Deviation 322298
|
1625609 ng·h/mL
Standard Deviation 142277
|
4190238 ng·h/mL
Standard Deviation 544757
|
PRIMARY outcome
Timeframe: 0 to 28 days post final dose and follow-up examinations (1 month and 2 months after the end of the post-dosing observation period).Population: t1/2
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
Outcome measures
| Measure |
KW-0761
n=3 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
n=4 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2)
|
179 hours
Standard Deviation 40
|
201 hours
Standard Deviation 196
|
332 hours
Standard Deviation 122
|
462 hours
Standard Deviation 51
|
SECONDARY outcome
Timeframe: 50 daysThe 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).
Outcome measures
| Measure |
KW-0761
n=3 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
n=4 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 Participants
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Antitumor Effect
Not Evaluable (NE)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Antitumor Effect
Complete Response (CR)
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Antitumor Effect
Uncertain Complete Response (CRu)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Antitumor Effect
Partial Response (PR)
|
1 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Antitumor Effect
Stable Disease (SD)
|
1 participants
|
2 participants
|
0 participants
|
2 participants
|
|
Antitumor Effect
Progressive Disease (PD)
|
1 participants
|
1 participants
|
3 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to responseTTP was defined as the period from the day starting the first KW-0761 dosing to the day of PD identification (or the day of death if the subject died before PD was documented). Subjects were to be censored at the time of starting post-treatment, if it was started before PD identification.
Outcome measures
| Measure |
KW-0761
n=16 Participants
KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
|
KW-0761 0.1mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Time to Progression (TTP)
|
46.5 days
Interval 8.0 to 617.0
|
—
|
—
|
—
|
Adverse Events
KW-0761 0.01mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
KW-0761 0.1mg
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
KW-0761 0.5mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
KW-0761 1.0mg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
KW-0761 0.01mg
n=3 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.1mg
n=4 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
Infections and infestations
Herpes zoster
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
Other adverse events
| Measure |
KW-0761 0.01mg
n=3 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.1mg
n=4 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 0.5mg
n=3 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
KW-0761 1.0mg
n=6 participants at risk
IV infusions of KW-0761 once/week for 4 weeks
|
|---|---|---|---|---|
|
General disorders
Infusion-related reaction
|
100.0%
3/3 • Number of events 3 • 28 days
|
75.0%
3/4 • Number of events 3 • 28 days
|
100.0%
3/3 • Number of events 3 • 28 days
|
66.7%
4/6 • Number of events 4 • 28 days
|
|
Immune system disorders
Cytokine release syndrome
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Infections and infestations
Skin infection
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
33.3%
2/6 • Number of events 2 • 28 days
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
33.3%
2/6 • Number of events 2 • 28 days
|
|
Investigations
Blood albumin decreased
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
33.3%
2/6 • Number of events 2 • 28 days
|
|
Investigations
Blood pressure increased
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Blood sodium increased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Electrocardiogram QT prolonged
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Blood urine present
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Heart rate increased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • Number of events 2 • 28 days
|
100.0%
4/4 • Number of events 4 • 28 days
|
100.0%
3/3 • Number of events 3 • 28 days
|
100.0%
6/6 • Number of events 6 • 28 days
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Number of events 1 • 28 days
|
50.0%
2/4 • Number of events 2 • 28 days
|
100.0%
3/3 • Number of events 3 • 28 days
|
66.7%
4/6 • Number of events 4 • 28 days
|
|
Investigations
Neutrophil count increased
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Platelet count decreased
|
100.0%
3/3 • Number of events 3 • 28 days
|
50.0%
2/4 • Number of events 2 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
50.0%
3/6 • Number of events 3 • 28 days
|
|
Investigations
Protein total decreased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Weight decreased
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Weight increased
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
White blood cell count decreased
|
33.3%
1/3 • Number of events 1 • 28 days
|
50.0%
2/4 • Number of events 2 • 28 days
|
100.0%
3/3 • Number of events 3 • 28 days
|
66.7%
4/6 • Number of events 4 • 28 days
|
|
Investigations
White blood cell count increased
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Eosinophil percentage increased
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Investigations
Blood alkaline phosphatase increased
|
33.3%
1/3 • Number of events 1 • 28 days
|
50.0%
2/4 • Number of events 2 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Investigations
Platelet function test abnormal
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Nervous system disorders
Sensory disturbance
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/6 • 28 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
33.3%
2/6 • Number of events 2 • 28 days
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Blood and lymphatic system disorders
Lymph node pain
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3 • 28 days
|
75.0%
3/4 • Number of events 3 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Cardiac disorders
Left ventricular dysfunction
|
66.7%
2/3 • Number of events 2 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
0.00%
0/6 • 28 days
|
|
General disorders
Chills
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
0.00%
0/3 • 28 days
|
33.3%
2/6 • Number of events 2 • 28 days
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1 • 28 days
|
25.0%
1/4 • Number of events 1 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
|
General disorders
Malaise
|
0.00%
0/3 • 28 days
|
0.00%
0/4 • 28 days
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/6 • 28 days
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Number of events 1 • 28 days
|
0.00%
0/4 • 28 days
|
66.7%
2/3 • Number of events 2 • 28 days
|
16.7%
1/6 • Number of events 1 • 28 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER