Trial Outcomes & Findings for Phase II Study of KW-0761 in Subjects With CCR4-positive Adult T-cell Leukemia-lymphoma (NCT NCT00920790)
NCT ID: NCT00920790
Last Updated: 2017-03-29
Results Overview
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.
COMPLETED
PHASE2
28 participants
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.
2017-03-29
Participant Flow
Participants were enrolled from 1 June 2009 through 9 November 2010
Participant milestones
| Measure |
KW-0761
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Overall Study
STARTED
|
27
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
14
|
Reasons for withdrawal
| Measure |
KW-0761
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Overall Study
aggravation of general condition
|
14
|
Baseline Characteristics
Phase II Study of KW-0761 in Subjects With CCR4-positive Adult T-cell Leukemia-lymphoma
Baseline characteristics by cohort
| Measure |
KW-0761
n=27 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Age, Continuous
|
64 years
FULL_RANGE 7.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
KW-0761
n=26 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Overall Response Rate (ORR)
|
50 percentage of participants with response
Interval 29.9 to 70.1
|
PRIMARY outcome
Timeframe: 0 to 7 days post final dosePopulation: Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
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.
Outcome measures
| Measure |
KW-0761
n=27 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Pharmacokinetics-Plasma KW-0761 Concentrations
Cmax
|
42943.2 ng/mL
Standard Deviation 14239.5
|
|
Pharmacokinetics-Plasma KW-0761 Concentrations
Ctrough
|
33638.3 ng/mL
Standard Deviation 10572.2
|
PRIMARY outcome
Timeframe: 0 to 7 days post final dosePopulation: Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
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.
Outcome measures
| Measure |
KW-0761
n=27 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days)
|
6297408 ng·h/mL
Standard Deviation 1812467
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
KW-0761
n=27 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Pharmacokinetics-Plasma KW-0761 Concentrations (t1/2)
|
422 hours
Standard Deviation 147
|
SECONDARY outcome
Timeframe: Baseline to responsePopulation: Of the 27 subjects enrolled, 26 were included in the efficacy analysis set, whereas 1 was excluded.
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).
Outcome measures
| Measure |
KW-0761
n=26 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Progression Free Survival (PFS)
|
97 days
Interval 12.0 to 401.0
|
SECONDARY outcome
Timeframe: Baseline to responsePopulation: Of the 27 subjects enrolled, 26 were included in the overall survival analysis set, whereas 1 was excluded.
The time from the date of first KW-0761 dosing to the date of death.
Outcome measures
| Measure |
KW-0761
n=26 Participants
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Overall Survival (OS)
|
176.5 days
Interval 101.0 to 401.0
|
Adverse Events
KW-0761
Serious adverse events
| Measure |
KW-0761
n=27 participants at risk
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.8%
4/27
|
|
Infections and infestations
Pharyngitis
|
3.7%
1/27
|
Other adverse events
| Measure |
KW-0761
n=27 participants at risk
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
|
|---|---|
|
Cardiac disorders
Tachycardia
|
29.6%
8/27
|
|
Cardiac disorders
Ventricular extrasystoles
|
7.4%
2/27
|
|
Cardiac disorders
Cardiac failure congestive
|
3.7%
1/27
|
|
Cardiac disorders
Left ventricular dysfunction
|
3.7%
1/27
|
|
Ear and labyrinth disorders
Hypoacusis
|
3.7%
1/27
|
|
Cardiac disorders
Left atrial dilatation
|
3.7%
1/27
|
|
Eye disorders
Conjunctivitis
|
3.7%
1/27
|
|
Eye disorders
Eye pruritus
|
3.7%
1/27
|
|
Gastrointestinal disorders
Nausea
|
18.5%
5/27
|
|
Gastrointestinal disorders
Vomiting
|
18.5%
5/27
|
|
Gastrointestinal disorders
Constipation
|
11.1%
3/27
|
|
Gastrointestinal disorders
Diarrhoea
|
3.7%
1/27
|
|
Gastrointestinal disorders
Gastritis
|
3.7%
1/27
|
|
General disorders
Pyrexia
|
85.2%
23/27
|
|
General disorders
Chills
|
59.3%
16/27
|
|
General disorders
Malaise
|
7.4%
2/27
|
|
General disorders
Oedema peripheral
|
7.4%
2/27
|
|
General disorders
Application site erythema
|
3.7%
1/27
|
|
General disorders
Hypothermia
|
3.7%
1/27
|
|
General disorders
Pain
|
3.7%
1/27
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
7.4%
2/27
|
|
Hepatobiliary disorders
Cholangitis
|
3.7%
1/27
|
|
Immune system disorders
Sarcoidosis
|
3.7%
1/27
|
|
Infections and infestations
Nasopharyngitis
|
14.8%
4/27
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
3.7%
1/27
|
|
Infections and infestations
Cytomegalovirus infection
|
3.7%
1/27
|
|
Infections and infestations
Urinary tract infection
|
3.7%
1/27
|
|
Infections and infestations
Oral herpes
|
3.7%
1/27
|
|
Injury, poisoning and procedural complications
Thermal burn
|
3.7%
1/27
|
|
Investigations
Lymphocyte count decreased
|
96.3%
26/27
|
|
Investigations
White blood cell count decreased
|
66.7%
18/27
|
|
Investigations
Neutrophil count decreased
|
51.9%
14/27
|
|
Investigations
Platelet count decreased
|
51.9%
14/27
|
|
Investigations
Alanine aminotransferase increased
|
40.7%
11/27
|
|
Investigations
Aspartate aminotransferase increased
|
40.7%
11/27
|
|
Investigations
Blood lactate dehydrogenase increased
|
37.0%
10/27
|
|
Investigations
Haemoglobin decreased
|
29.6%
8/27
|
|
Investigations
Blood alkaline phosphatase increased
|
25.9%
7/27
|
|
Investigations
Blood creatinine increased
|
22.2%
6/27
|
|
Investigations
Blood pressure increased
|
22.2%
6/27
|
|
Investigations
Weight increased
|
22.2%
6/27
|
|
Investigations
Blood albumin decreased
|
18.5%
5/27
|
|
Investigations
Blood sodium decreased
|
14.8%
4/27
|
|
Investigations
Gamma-glutamyltransferase increased
|
14.8%
4/27
|
|
Investigations
Weight decreased
|
14.8%
4/27
|
|
Investigations
Blood pressure decreased
|
11.1%
3/27
|
|
Investigations
Protein total decreased
|
11.1%
3/27
|
|
Investigations
Red blood cell count decreased
|
11.1%
3/27
|
|
Investigations
Blood phosphorus decreased
|
11.1%
3/27
|
|
Investigations
Blood chloride increased
|
7.4%
2/27 • Number of events 2
|
|
Investigations
Haematocrit decreased
|
7.4%
2/27 • Number of events 2
|
|
Investigations
Blood urine present
|
7.4%
2/27 • Number of events 2
|
|
Investigations
Eosinophil percentage increased
|
7.4%
2/27 • Number of events 2
|
|
Investigations
Blood calcium decreased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Blood potassium decreased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Blood urea increased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
C-reactive protein increased
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Glucose urine present
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Heart rate increased
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
25.9%
7/27 • Number of events 7
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
18.5%
5/27 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
18.5%
5/27 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
18.5%
5/27 • Number of events 5
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
14.8%
4/27 • Number of events 4
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.1%
3/27 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.4%
2/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.4%
2/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperammonaemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypochloraemia
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.4%
2/27 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.7%
1/27
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
3.7%
1/27
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.7%
1/27
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.7%
1/27
|
|
Nervous system disorders
Headache
|
11.1%
3/27
|
|
Nervous system disorders
Hypoaesthesia
|
7.4%
2/27
|
|
Nervous system disorders
Dysgeusia
|
3.7%
1/27
|
|
Nervous system disorders
Mononeuritis
|
3.7%
1/27
|
|
Nervous system disorders
Movement disorder
|
3.7%
1/27
|
|
Nervous system disorders
Somnolence
|
3.7%
1/27
|
|
Psychiatric disorders
Disorientation
|
3.7%
1/27
|
|
Psychiatric disorders
Insomnia
|
14.8%
4/27
|
|
Renal and urinary disorders
Proteinuria
|
14.8%
4/27
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
18.5%
5/27
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal stenosis
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.7%
1/27
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.7%
1/27
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.7%
1/27
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.8%
4/27
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.4%
2/27
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Eczema nummular
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.7%
1/27
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
3.7%
1/27
|
|
Vascular disorders
Hypertension
|
7.4%
2/27
|
|
Vascular disorders
Hot flush
|
7.4%
2/27
|
|
Vascular disorders
Flushing
|
3.7%
1/27
|
|
Vascular disorders
Hypotension
|
3.7%
1/27
|
|
Vascular disorders
Peripheral circulatory failure
|
3.7%
1/27
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
3.7%
1/27
|
|
General disorders
Infusion related reaction
|
88.9%
24/27
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER