Peripheral T-Cell LymphomaPhase 1/2NCT00888927
Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma
A Phase 1/2 study testing KW-0761 in people with Peripheral T-Cell Lymphoma, run by Kyowa Kirin Co., Ltd. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral T-Cell Lymphoma
- What is being tested?
- KW-0761
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2009to Sep 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
M.D.Anderson Cancer Center
Houston, Texas, 77030
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Yale Comprehensive Cancer Center
New Haven, Connecticut, 06519
Stanford Medical Center
Stanford, California, 94305
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
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
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.
Read the 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.
- Conditions
- Peripheral T-Cell Lymphoma
- Being tested
- KW-0761
- Keywords
- T-Cell Lymphoma, PTCL, CTCL
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KW-0761Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: KW-0761 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (1)
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.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral T-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Kyowa Kirin Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Responsible party
- Sponsor
- Investigators
- Michael Kurman, MD, Study director, Kyowa Hakko Kirin Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00888927
- Sponsor's protocol ID
- KW-0761-001
- Status last verified
- Apr 2024
- First submitted
- 27 Apr 2009
- Last updated
- 25 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 25605368
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00888927
- Acronym / sponsor ID
- KW-0761-001
- Conditions
- Peripheral T-Cell Lymphoma
- Keywords
- T-Cell Lymphoma, PTCL, CTCL
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Study start
- May 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 28 Apr 2009 (estimated)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Cohort 1 | Experimental | Biological: KW-0761First 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 |
| Phase 1 Cohort 2 | Experimental | Biological: KW-0761First 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 |
| Phase 1 Cohort 3 | Experimental | Biological: KW-0761First 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 |
| Phase 2 | Experimental | Biological: KW-0761First course: Maximum tolerated dose once a week over 1 hour for 4 weeks Subsequent courses: Maximum tolerated dose over 1 hour every other week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KW-0761The 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. | Biological | Phase 1 Cohort 1, Phase 1 Cohort 2, Phase 1 Cohort 3, Phase 2 |
Primary outcome
Maximum Tolerated Dose
Time frame: 6 weeks
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.
1 secondary outcome
Overall Response Rate (ORR)
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25605368Duvic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Kurman, MD study director
Kyowa Hakko Kirin Pharma, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KW-0761 in people with Peripheral T-Cell Lymphoma, run by Kyowa Kirin Co., Ltd. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00888927, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2024.