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

• Sponsor: Kyowa Kirin Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00920790
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adult T-cell Leukemia-lymphoma	Biological: KW-0761	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Study of KW-0761 in Patients With CCR4-Positive Adult T-cell Leukemia-Lymphoma
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KW-0761	Biological: KW-0761; KW-0761 is administered weekly for 8 weeks as an intravenous infusion of 2 hours at a dose of 1.0 mg/kg.; Other Names: Mogamulizumab

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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

1. 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).

2. Overall Survival (OS) [Baseline to response]

   The time from the date of first KW-0761 dosing to the date of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tokyo		Japan

Sponsors and Collaborators

• Kyowa Kirin Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kyowa Kirin Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00920790
• Other Study ID Numbers: 0761-002
• First Posted: Jun 15, 2009
• Last Update Posted: Mar 29, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Mogamulizumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 1 June 2009 through 9 November 2010

Arm/Group Title	KW-0761
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

Baseline Characteristics

Arm/Group Title	KW-0761
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Overall Participants	27
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64 (7.5)
Sex: Female, Male (Count of Participants)
Female	15 55.6%
Male	12 44.4%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
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.

Outcome Measure Data

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
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	26
Number (95% Confidence Interval) [percentage of participants with response]	50 185.2%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
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

Outcome Measure Data

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
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	26
Median (Full Range) [days]	97

3. Secondary Outcome

Title	Overall Survival (OS)
Description	The time from the date of first KW-0761 dosing to the date of death.
Time Frame	Baseline to response

Outcome Measure Data

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
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	26
Median (Full Range) [days]	176.5

4. Primary Outcome

Title	Pharmacokinetics-Plasma KW-0761 Concentrations
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

Outcome Measure Data

Analysis Population Description

Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.

Arm/Group Title	KW-0761
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	27
Cmax	42943.2 (14239.5)
Ctrough	33638.3 (10572.2)

5. Primary Outcome

Title	Pharmacokinetics-Plasma KW-0761 Concentrations (AUC0-7days)
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

Outcome Measure Data

Analysis Population Description

Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.

Arm/Group Title	KW-0761
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	27
Mean (Standard Deviation) [ng·h/mL]	6297408 (1812467)

6. Primary Outcome

Title	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).

Outcome Measure Data

Analysis Population Description

Of the 27 subjects enrolled, 27 were included in the pharmacokinetics analysis set.

Arm/Group Title	KW-0761
Arm/Group Description	IV infusions of KW-0761 once/week for 8 weeks at a dose of 1.0mg/kg
Measure Participants	27
Mean (Standard Deviation) [hours]	422 (147)

Adverse Events

Arm/Group Title	KW-0761
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	KW-0761
	Affected / at Risk (%)	# Events
Total	6/27 (22.2%)
Infections and infestations
Pharyngitis	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	1/27 (3.7%)
Rash	4/27 (14.8%)
Other (Not Including Serious) Adverse Events
	KW-0761
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/27 (3.7%)
Cardiac disorders
Tachycardia	8/27 (29.6%)
Ventricular extrasystoles	2/27 (7.4%)
Cardiac failure congestive	1/27 (3.7%)
Left ventricular dysfunction	1/27 (3.7%)
Left atrial dilatation	1/27 (3.7%)
Ear and labyrinth disorders
Hypoacusis	1/27 (3.7%)
Eye disorders
Conjunctivitis	1/27 (3.7%)
Eye pruritus	1/27 (3.7%)
Gastrointestinal disorders
Nausea	5/27 (18.5%)
Vomiting	5/27 (18.5%)
Constipation	3/27 (11.1%)
Diarrhoea	1/27 (3.7%)
Gastritis	1/27 (3.7%)
General disorders
Pyrexia	23/27 (85.2%)
Chills	16/27 (59.3%)
Malaise	2/27 (7.4%)
Oedema peripheral	2/27 (7.4%)
Application site erythema	1/27 (3.7%)
Hypothermia	1/27 (3.7%)
Pain	1/27 (3.7%)
Infusion related reaction	24/27 (88.9%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/27 (7.4%)
Cholangitis	1/27 (3.7%)
Immune system disorders
Sarcoidosis	1/27 (3.7%)
Infections and infestations
Nasopharyngitis	4/27 (14.8%)
Bronchopulmonary aspergillosis	1/27 (3.7%)
Cytomegalovirus infection	1/27 (3.7%)
Urinary tract infection	1/27 (3.7%)
Oral herpes	1/27 (3.7%)
Injury, poisoning and procedural complications
Thermal burn	1/27 (3.7%)
Investigations
Lymphocyte count decreased	26/27 (96.3%)
White blood cell count decreased	18/27 (66.7%)
Neutrophil count decreased	14/27 (51.9%)
Platelet count decreased	14/27 (51.9%)
Alanine aminotransferase increased	11/27 (40.7%)
Aspartate aminotransferase increased	11/27 (40.7%)
Blood lactate dehydrogenase increased	10/27 (37%)
Haemoglobin decreased	8/27 (29.6%)
Blood alkaline phosphatase increased	7/27 (25.9%)
Blood creatinine increased	6/27 (22.2%)
Blood pressure increased	6/27 (22.2%)
Weight increased	6/27 (22.2%)
Blood albumin decreased	5/27 (18.5%)
Blood sodium decreased	4/27 (14.8%)
Gamma-glutamyltransferase increased	4/27 (14.8%)
Weight decreased	4/27 (14.8%)
Blood pressure decreased	3/27 (11.1%)
Protein total decreased	3/27 (11.1%)
Red blood cell count decreased	3/27 (11.1%)
Blood phosphorus decreased	3/27 (11.1%)
Blood chloride increased	2/27 (7.4%)	2
Haematocrit decreased	2/27 (7.4%)	2
Blood urine present	2/27 (7.4%)	2
Eosinophil percentage increased	2/27 (7.4%)	2
Blood calcium decreased	1/27 (3.7%)	1
Blood potassium decreased	1/27 (3.7%)	1
Blood urea increased	1/27 (3.7%)	1
C-reactive protein increased	1/27 (3.7%)	1
Glucose urine present	1/27 (3.7%)	1
Heart rate increased	1/27 (3.7%)	1
Metabolism and nutrition disorders
Hypoalbuminaemia	7/27 (25.9%)	7
Hypercalcaemia	5/27 (18.5%)	5
Hypokalaemia	5/27 (18.5%)	5
Hypophosphataemia	5/27 (18.5%)	5
Hyperuricaemia	4/27 (14.8%)	4
Decreased appetite	3/27 (11.1%)	3
Hypocalcaemia	2/27 (7.4%)	2
Hyponatraemia	2/27 (7.4%)	2
Hyperammonaemia	1/27 (3.7%)	1
Hyperglycaemia	1/27 (3.7%)	1
Hypernatraemia	1/27 (3.7%)	1
Hypochloraemia	1/27 (3.7%)	1
Metabolic acidosis	1/27 (3.7%)	1
Tumour lysis syndrome	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Neck pain	2/27 (7.4%)	2
Arthralgia	1/27 (3.7%)
Arthritis	1/27 (3.7%)
Musculoskeletal pain	1/27 (3.7%)
Pain in extremity	1/27 (3.7%)
Nervous system disorders
Headache	3/27 (11.1%)
Hypoaesthesia	2/27 (7.4%)
Dysgeusia	1/27 (3.7%)
Mononeuritis	1/27 (3.7%)
Movement disorder	1/27 (3.7%)
Somnolence	1/27 (3.7%)
Psychiatric disorders
Disorientation	1/27 (3.7%)
Insomnia	4/27 (14.8%)
Renal and urinary disorders
Proteinuria	4/27 (14.8%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	5/27 (18.5%)
Nasal congestion	2/27 (7.4%)
Pleural effusion	2/27 (7.4%)
Wheezing	2/27 (7.4%)
Tracheal stenosis	2/27 (7.4%)
Oropharyngeal pain	2/27 (7.4%)
Cough	1/27 (3.7%)
Dysphonia	1/27 (3.7%)
Epistaxis	1/27 (3.7%)
Oropharyngeal discomfort	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Pruritus	4/27 (14.8%)
Hyperhidrosis	2/27 (7.4%)
Dermatitis	1/27 (3.7%)
Dermatitis contact	1/27 (3.7%)
Eczema	1/27 (3.7%)
Eczema nummular	1/27 (3.7%)
Erythema	1/27 (3.7%)
Erythema nodosum	1/27 (3.7%)
Vascular disorders
Hypertension	2/27 (7.4%)
Hot flush	2/27 (7.4%)
Flushing	1/27 (3.7%)
Hypotension	1/27 (3.7%)
Peripheral circulatory failure	1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.