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Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma

Primary Purpose

Peripheral T-Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KW-0761
Sponsored by
Kyowa Hakko Kirin Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral T-Cell Lymphoma focused on measuring T-Cell Lymphoma, PTCL, CTCL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. histologically/cytologically confirmed diagnosis of PTCL including CTCL (including MF and SS) but excluding ATLL.
  2. failed at least one prior systemic therapy for PTCL or CTCL.
  3. ECOG PS of <=2 at study entry.
  4. >=18 years of age.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. serum creatinine ≤1.5 x ULN or a calculated creatinine clearance >60 mL/min.
  10. CTCL subjects previously treated with zanolimumab are eligible provided their CD4+ cell counts have recovered to pre-treatment levels.
  11. Subjects with MF and a history of staphylococcus colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics.
  12. provided signed informed consent.
  13. WOCBP must have a negative pregnancy test within 7 days of receiving study medication.
  14. WOCBP must agree to use effective contraception
  15. 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:

  1. 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.
  2. has known or tests positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B or hepatitis C.
  3. has evidence of central nervous system (CNS) metastasis.
  4. has received monoclonal antibodies within 6 weeks of study entry.
  5. is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
  6. 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.
  7. 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.
  8. has experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.
  9. 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.
  10. Subjects with known autoimmune diseases. Subjects with Hashimoto's thyroiditis controlled with medication are eligible for enrollment.

Sites / Locations

  • Ronald Reagan UCLA Medical Center
  • Stanford Medical Center
  • Yale Comprehensive Cancer Center
  • H. Lee Moffitt Cancer Center and Research Institute
  • M.D.Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1 Cohort 1

Phase 1 Cohort 2

Phase 1 Cohort 3

Phase 2

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
April 27, 2009
Last Updated
December 3, 2020
Sponsor
Kyowa Hakko Kirin Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00888927
Brief Title
Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma
Official Title
Open-Label, Multi-Center, Dose Escalation Phase 1/2 Study of Anti-CCR4 Monoclonal Antibody KW-0761 as Monotherapy in Subjects With Previously Treated Peripheral T-Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Hakko Kirin Pharma, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will determine the maximum dose of KW-0761 administered intravenously that can be given safely in subjects with previously treated peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma(CTCL)and will see if it is effective in treating the disease.
Detailed Description
This Phase 1/2, multicenter, open-label, dose escalation clinical study will enroll up to 47 subjects with previously treated PTCL including CTCL. The study is comprised of a dose escalation phase (Phase 1) and a preliminary assessment of efficacy (Phase 2). In the dose escalation phase, 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. During the first course of treatment if assessments performed at day 29 (end of week 4) indicate that a subject has demonstrated an overall CR, the subject may continue on study for up to an additional four infusions beyond CR on an every other week infusion schedule. Treatment will then be discontinued in order to determine duration of response. If a subject experiences a PR or SD, the subject may continue therapy after consultation between the investigator and the medical monitor on an every other week infusion schedule until disease progression occurs or other withdrawal criteria are met.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral T-Cell Lymphoma
Keywords
T-Cell Lymphoma, PTCL, CTCL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Cohort 1
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 1 Cohort 2
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 1 Cohort 3
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
KW-0761
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
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.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Kurman, MD
Organizational Affiliation
Kyowa Hakko Kirin Pharma, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Yale Comprehensive Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
M.D.Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25605368
Citation
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.
Results Reference
derived
Links:
URL
https://ashpublications.org/blood/article/125/12/1883/33700/Phase-1-2-study-of-mogamulizumab-a-defucosylated
Description
Blood Journal March 19, 2015: Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

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Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma

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