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

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ClinicalTrials.gov Identifier: NCT00920790
Recruitment Status : Completed
First Posted : June 15, 2009
Results First Posted : September 25, 2012
Last Update Posted : March 29, 2017
Sponsor:
Information provided by (Responsible Party):
Kyowa Hakko Kirin Co., Ltd

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Adult T-cell Leukemia-lymphoma
Intervention Biological: KW-0761
Enrollment 28
Recruitment Details Participants were enrolled from 1 June 2009 through 9 November 2010
Pre-assignment Details  
Arm/Group Title KW-0761
Hide Arm/Group Description IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Period Title: Overall Study
Started 27
Completed 13
Not Completed 14
Reason Not Completed
aggravation of general condition             14
Arm/Group Title KW-0761
Hide Arm/Group Description IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Baseline Participants 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 27 participants
64
(49 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Female
15
  55.6%
Male
12
  44.4%
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description

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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 26 were included in the efficacy analysis set, whereas 1 was excluded.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants with response
50
(29.9 to 70.1)
2.Primary Outcome
Title Pharmacokinetics-Plasma KW-0761 Concentrations
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax 42943.2  (14239.5)
Ctrough 33638.3  (10572.2)
3.Primary Outcome
Title Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: ng·h/mL
6297408  (1812467)
4.Primary Outcome
Title Pharmacokinetics-Plasma KW-0761 Concentrations (t1/2)
Hide Description [Not Specified]
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).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: hours
422  (147)
5.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 26 were included in the efficacy analysis set, whereas 1 was excluded.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 26
Median (Full Range)
Unit of Measure: days
97
(12 to 401)
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description The time from the date of first KW-0761 dosing to the date of death.
Time Frame Baseline to response
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 27 subjects enrolled, 26 were included in the overall survival analysis set, whereas 1 was excluded.
Arm/Group Title KW-0761
Hide Arm/Group Description:
IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Number of Participants Analyzed 26
Median (Full Range)
Unit of Measure: days
176.5
(101 to 401)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title KW-0761
Hide Arm/Group Description IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
All-Cause Mortality
KW-0761
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
KW-0761
Affected / at Risk (%) # Events
Total   6/27 (22.22%)    
Infections and infestations   
Pharyngitis * 1  1/27 (3.70%) 
Skin and subcutaneous tissue disorders   
Stevens-Johnson syndrome * 1  1/27 (3.70%) 
Rash * 1  4/27 (14.81%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA/J ver. 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
KW-0761
Affected / at Risk (%) # Events
Total   27/27 (100.00%)    
Blood and lymphatic system disorders   
Disseminated intravascular coagulation * 1  1/27 (3.70%) 
Cardiac disorders   
Tachycardia * 1  8/27 (29.63%) 
Ventricular extrasystoles * 1  2/27 (7.41%) 
Cardiac failure congestive * 1  1/27 (3.70%) 
Left ventricular dysfunction * 1  1/27 (3.70%) 
Left atrial dilatation * 1  1/27 (3.70%) 
Ear and labyrinth disorders   
Hypoacusis * 1  1/27 (3.70%) 
Eye disorders   
Conjunctivitis * 1 [1]  1/27 (3.70%) 
Eye pruritus * 1  1/27 (3.70%) 
Gastrointestinal disorders   
Nausea * 1  5/27 (18.52%) 
Vomiting * 1  5/27 (18.52%) 
Constipation * 1  3/27 (11.11%) 
Diarrhoea * 1  1/27 (3.70%) 
Gastritis * 1  1/27 (3.70%) 
General disorders   
Pyrexia * 1  23/27 (85.19%) 
Chills * 1  16/27 (59.26%) 
Malaise * 1  2/27 (7.41%) 
Oedema peripheral * 1  2/27 (7.41%) 
Application site erythema * 1  1/27 (3.70%) 
Hypothermia * 1  1/27 (3.70%) 
Pain * 1  1/27 (3.70%) 
Infusion related reaction * 1  24/27 (88.89%) 
Hepatobiliary disorders   
Hyperbilirubinaemia * 1  2/27 (7.41%) 
Cholangitis * 1  1/27 (3.70%) 
Immune system disorders   
Sarcoidosis * 1  1/27 (3.70%) 
Infections and infestations   
Nasopharyngitis * 1  4/27 (14.81%) 
Bronchopulmonary aspergillosis * 1  1/27 (3.70%) 
Cytomegalovirus infection * 1  1/27 (3.70%) 
Urinary tract infection * 1  1/27 (3.70%) 
Oral herpes * 1  1/27 (3.70%) 
Injury, poisoning and procedural complications   
Thermal burn * 1  1/27 (3.70%) 
Investigations   
Lymphocyte count decreased * 1  26/27 (96.30%) 
White blood cell count decreased * 1  18/27 (66.67%) 
Neutrophil count decreased * 1  14/27 (51.85%) 
Platelet count decreased * 1  14/27 (51.85%) 
Alanine aminotransferase increased * 1  11/27 (40.74%) 
Aspartate aminotransferase increased * 1  11/27 (40.74%) 
Blood lactate dehydrogenase increased * 1  10/27 (37.04%) 
Haemoglobin decreased * 1  8/27 (29.63%) 
Blood alkaline phosphatase increased * 1  7/27 (25.93%) 
Blood creatinine increased * 1  6/27 (22.22%) 
Blood pressure increased * 1  6/27 (22.22%) 
Weight increased * 1  6/27 (22.22%) 
Blood albumin decreased * 1  5/27 (18.52%) 
Blood sodium decreased * 1  4/27 (14.81%) 
Gamma-glutamyltransferase increased * 1  4/27 (14.81%) 
Weight decreased * 1  4/27 (14.81%) 
Blood pressure decreased * 1  3/27 (11.11%) 
Protein total decreased * 1  3/27 (11.11%) 
Red blood cell count decreased * 1  3/27 (11.11%) 
Blood phosphorus decreased * 1  3/27 (11.11%) 
Blood chloride increased * 1  2/27 (7.41%)  2
Haematocrit decreased * 1  2/27 (7.41%)  2
Blood urine present * 1  2/27 (7.41%)  2
Eosinophil percentage increased * 1  2/27 (7.41%)  2
Blood calcium decreased * 1  1/27 (3.70%)  1
Blood potassium decreased * 1  1/27 (3.70%)  1
Blood urea increased * 1  1/27 (3.70%)  1
C-reactive protein increased * 1  1/27 (3.70%)  1
Glucose urine present * 1  1/27 (3.70%)  1
Heart rate increased * 1  1/27 (3.70%)  1
Metabolism and nutrition disorders   
Hypoalbuminaemia * 1  7/27 (25.93%)  7
Hypercalcaemia * 1  5/27 (18.52%)  5
Hypokalaemia * 1  5/27 (18.52%)  5
Hypophosphataemia * 1  5/27 (18.52%)  5
Hyperuricaemia * 1  4/27 (14.81%)  4
Decreased appetite * 1  3/27 (11.11%)  3
Hypocalcaemia * 1  2/27 (7.41%)  2
Hyponatraemia * 1  2/27 (7.41%)  2
Hyperammonaemia * 1  1/27 (3.70%)  1
Hyperglycaemia * 1  1/27 (3.70%)  1
Hypernatraemia * 1  1/27 (3.70%)  1
Hypochloraemia * 1  1/27 (3.70%)  1
Metabolic acidosis * 1  1/27 (3.70%)  1
Tumour lysis syndrome * 1  1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders   
Neck pain * 1  2/27 (7.41%)  2
Arthralgia * 1  1/27 (3.70%) 
Arthritis * 1  1/27 (3.70%) 
Musculoskeletal pain * 1  1/27 (3.70%) 
Pain in extremity * 1  1/27 (3.70%) 
Nervous system disorders   
Headache * 1  3/27 (11.11%) 
Hypoaesthesia * 1  2/27 (7.41%) 
Dysgeusia * 1  1/27 (3.70%) 
Mononeuritis * 1  1/27 (3.70%) 
Movement disorder * 1  1/27 (3.70%) 
Somnolence * 1  1/27 (3.70%) 
Psychiatric disorders   
Disorientation * 1  1/27 (3.70%) 
Insomnia * 1  4/27 (14.81%) 
Renal and urinary disorders   
Proteinuria * 1  4/27 (14.81%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  5/27 (18.52%) 
Nasal congestion * 1  2/27 (7.41%) 
Pleural effusion * 1  2/27 (7.41%) 
Wheezing * 1  2/27 (7.41%) 
Tracheal stenosis * 1  2/27 (7.41%) 
Oropharyngeal pain * 1  2/27 (7.41%) 
Cough * 1  1/27 (3.70%) 
Dysphonia * 1  1/27 (3.70%) 
Epistaxis * 1  1/27 (3.70%) 
Oropharyngeal discomfort * 1  1/27 (3.70%) 
Skin and subcutaneous tissue disorders   
Pruritus * 1  4/27 (14.81%) 
Hyperhidrosis * 1  2/27 (7.41%) 
Dermatitis * 1  1/27 (3.70%) 
Dermatitis contact * 1  1/27 (3.70%) 
Eczema * 1  1/27 (3.70%) 
Eczema nummular * 1  1/27 (3.70%) 
Erythema * 1  1/27 (3.70%) 
Erythema nodosum * 1  1/27 (3.70%) 
Vascular disorders   
Hypertension * 1  2/27 (7.41%) 
Hot flush * 1  2/27 (7.41%) 
Flushing * 1  1/27 (3.70%) 
Hypotension * 1  1/27 (3.70%) 
Peripheral circulatory failure * 1  1/27 (3.70%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA/J ver. 13.0
[1]
Conjunctivitis
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Name/Title: Project Management Department, Development Division
Organization: Kyowa Hakko Kirin
Responsible Party: Kyowa Hakko Kirin Co., Ltd
ClinicalTrials.gov Identifier: NCT00920790     History of Changes
Other Study ID Numbers: 0761-002
First Submitted: June 9, 2009
First Posted: June 15, 2009
Results First Submitted: July 9, 2012
Results First Posted: September 25, 2012
Last Update Posted: March 29, 2017