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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

Phase 1/Phase 2
18 Years
Not Enrolling
Peripheral T-Cell Lymphoma

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Trial Information

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 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.

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

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

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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Michael Kurman, MD

Investigator Role:

Study Director

Investigator Affiliation:

Kyowa Hakko Kirin Pharma


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

September 2012

Related Keywords:

  • Peripheral T-cell Lymphoma
  • T-Cell Lymphoma
  • PTCL
  • CTCL
  • Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Peripheral



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
Yale Comprehensive Cancer CenterNew Haven, Connecticut  06520-8028
Stanford Medical CenterStanford, California  94303
Ronald Reagan UCLA Medical CenterLos Angeles, California  90095
M.D.Anderson Cancer CenterHouston, Texas  77030