Safety Study to Evaluate Monoclonal Antibody KW-0761 in S... | NCT00888927

NCT00888927

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Kyowa Hakko Kirin Pharma, Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1 Cohort 1	Experimental	First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week	Biological: KW-0761
Phase 1 Cohort 2	Experimental	First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week	Biological: KW-0761
Phase 1 Cohort 3	Experimental	First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week	Biological: KW-0761
Phase 2	Experimental	First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week	Biological: KW-0761

Interventions

Name	Type	Description	Arm Group Labels	Other Names
KW-0761	Biological	The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. Succeeding dose levels will include 0.3 and 1 mg/kg. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose	The objective was to find the maximum tolerated dose (MTD). In the dose escalation phase (Phase 1), the starting dose was 0.1 mg/kg administered intravenously once every week for four weeks, followed by a 2-week observation period in the first treatment course. Succeeding dose levels included 0.3 and 1.0 mg/kg. Standard 3+3 cohorts for safety and DLT detection were utilized. Each cohort consisted of at least three subjects. If Dose-Limiting Toxicity (DLT) was observed in 0/3 subjects, escalation to the next dose level occurred.	6 weeks

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate was determined based on the response in all compartments (lymph nodes, skin, and viscera) as follows: Complete Response (CR) = complete disappearance of all clinical evidence of disease; Partial Response (PR) = regression of measurable disease; Stable Disease (SD) = failure to attain CR, PR, or PD; Progressive Disease (PD) = PD in any compartment; Relapse = recurrence of disease in prior CR in any compartment.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

histologically/cytologically confirmed diagnosis of PTCL including CTCL (including MF and SS) but excluding ATLL.
failed at least one prior systemic therapy for PTCL or CTCL.
ECOG PS of <=2 at study entry.
>=18 years of age.
completed any prior therapy at least four weeks prior to entry; however, patients with rapidly progressive malignant disease may be enrolled prior to this period after discussion with the medical monitor.
resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the NCI-CTCAE, v.3.0 excluding the specifications required in 7 and 8 below.
adequate hematological function: absolute neutrophil count>=1,500 cells/uL and platelets >=100,000 cells/uL except in patients with known bone marrow involvement where absolute neutrophil count must be >=1,000 cells/uL and platelets >=75,000 cells/uL.
adequate hepatic function: bilirubin ≤ 1.5 times the specific institutional ULN; aspartate transaminase and alanine transaminase each ≤ 2.5 x ULN or ≤ 5.0 x ULN in the presence of known hepatic malignancy.
serum creatinine ≤1.5 x ULN or a calculated creatinine clearance >60 mL/min.
CTCL subjects previously treated with zanolimumab are eligible provided their CD4+ cell counts have recovered to pre-treatment levels.
Subjects with MF and a history of staphylococcus colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics.
provided signed informed consent.
WOCBP must have a negative pregnancy test within 7 days of receiving study medication.
WOCBP must agree to use effective contraception
Male subjects must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study.

Exclusion Criteria:

has a significant uncontrolled intercurrent illness including, but not limited to: uncontrolled infection requiring antibiotics; clinically significant cardiac disease (class III or IV of the New York Heart Association [NYHA] classification); unstable angina pectoris; angioplasty, stenting, or myocardial infarction within 6 months; uncontrolled hypertension (systolic blood pressure >160 mm Hg, diastolic BP >100 mmHg, found on two consecutive measurements separated by a 1-week period) despite two anti-hypertensive medications; clinically significant cardiac arrhythmia; or uncontrolled diabetes.
has known or tests positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B or hepatitis C.
has evidence of central nervous system (CNS) metastasis.
has received monoclonal antibodies within 6 weeks of study entry.
is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
Subjects on any immunomodulatory drug, (other than low dose corticosteroids equivalent to a daily dose of 10 mg of prednisone). Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
has a psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit his or her compliance with study requirements.
has experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.
Subjects with active herpes simplex or herpes zoster. Subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded. Subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study.
Subjects with known autoimmune diseases. Subjects with Hashimoto's thyroiditis controlled with medication are eligible for enrollment.

Name	Affiliation	Role
Michael Kurman, MD	Kyowa Hakko Kirin Pharma, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ronald Reagan UCLA Medical Center		Los Angeles	California	90095	United States
Stanford Medical Center

PubMed Identifier	Type	Citation	Retractions
25605368	Derived	Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YH. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood. 2015 Mar 19;125(12):1883-9. doi: 10.1182/blood-2014-09-600924. Epub 2015 Jan 20.

Arm/Group Information

ID	Title	Description
FG000	Phase 1 Cohort 1	First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
FG001	Phase 1 Cohort 2	First course: 0.3 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.3 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.3 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
FG002	Phase 1 Cohort 3	First course: 1.0 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 1.0 mg/kg over 1 hour every other week KW-0761: The starting dose will be 1.0 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.
FG003	Phase 2	First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase 1 Cohort 1	First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose

The objective was to find the maximum tolerated dose (MTD). In the dose escalation phase (Phase 1), the starting dose was 0.1 mg/kg administered intravenously once every week for four weeks, followed by a 2-week observation period in the first treatment course. Succeeding dose levels included 0.3 and 1.0 mg/kg. Standard 3+3 cohorts for safety and DLT detection were utilized. Each cohort consisted of at least three subjects. If Dose-Limiting Toxicity (DLT) was observed in 0/3 subjects, escalation to the next dose level occurred.

Safety Analysis set - Included all subjects who received at least one dose of KW-0761 (even a partial dose)

Posted

Count of Participants

Participants

6 weeks

ID	Title	Description
OG000	Phase 1 Cohort 1	First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1 Cohort 1	First course: 0.1 mg/kg once a week over 1 hour for 4 weeks Subsequent courses: 0.1 mg/kg over 1 hour every other week KW-0761: The starting dose will be 0.1 mg/kg administered i.v. once every week for four weeks, followed by a 2-week observation period in the first treatment course. If a subject has demonstrated an overall CR, may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. If a subject experiences a PR or SD, the subject may continue therapy on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

ID	Term
D016411	Lymphoma, T-Cell, Peripheral
D016399	Lymphoma, T-Cell

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms