Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL

NCT ID: NCT00355472

Last Updated: 2012-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2008-10-31

Brief Summary

This is a Phase I label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell lymphoma (PTCL).

Detailed Description

This is a Phase I open-label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL). This study is designed to evaluate safety, pharmacokinetics, immunogenicity and preliminary efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose (RPIID) have been established.

Conditions

Adult T-Cell Leukemia and Lymphoma (ATL); Adult Peripheral T-Cell Lymphoma (PTCL)

Keywords

Adult T-Cell Leukemia; ATL; Adult Peripheral T-Cell Lymphoma; PTCL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

KW-0761

Group Type: EXPERIMENTAL

KW-0761

Intervention Type: DRUG

IV administration at 4 escalating dose levels.

Interventions

KW-0761

IV administration at 4 escalating dose levels.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed diagnosis of a CCR4-positive ATL and PTCL that is any of the following:

A. ATL (Adult T-Cell Leukemia-Lymphoma)

• Seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody;
• Acute, Lymphoma, or Chronic phase with high-risk factors (within 14 days before the study entry);

B. PTCL (Peripheral T-Cell Lymphoma)

• Includes Mycosis Fungoides and Sezary Syndrome;

2: Relapsed to the latest standard chemotherapy;

3: Received at least one prior chemotherapy;

4: After 4 weeks from a prior therapy;

5: Have measurable disease;

6:Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;

7: Male or female, at least 20 years and not older than 70 years of age;

8: Signed written informed consent;

9: Stay in hospital for 4 weeks;

10: HBs antigen: negative, HBV-DNA: below the limit of quantification (within 14 days before the study entry);

11: Adequate bone marrow, hepatic and cardiac function including the followings:

• Neutrophil count ≥ 1,500 /mm3,
• Platelets ≥ 75,000 /mm3,
• Hemoglobin ≥ 8.0 g/dL
• Serum creatinine ≤ 1.5 x ULN;
• Serum SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5.0 x ULN if considered due to disease involvement in liver);
• Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if considered due to disease involvement in liver)
• Serum calcium ≤ 11.0 mg/dL
• PaO2 ≥ 65 mmHg or SaO2 ≥ 90%
• No clinically significant Electrocardiogram abnormality
• Left Ventricular Ejection Fraction ≥ 50% [by ECHO or MUGA]

Exclusion Criteria

1. Co-existing active infection or any co-existing medical condition that may compromise the safety of patients during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results;

2. Active tuberculosis;

3. Prior stem cell transplantation;

4. Myocardial infarction (within 12 months prior to the study entry);

5. Concurrent acute or chronic hepatitis, or cirrhosis;

6. Anti-HCV: positive, Anti-HIV: positive

7. Concurrent active malignant disease;

8. Known allergic reaction to antibody therapy;

9. Concomitant treatment with systemic steroids;

10. Prior and Concurrent psychiatric disorder including dementia, epilepsy or any other CNS diseases;

11. Evidence of CNS metastasis at baseline;

12. Prior and Concurrent spinal cord disease;

13. Radiation therapy for bulky mass disease at the time of study entry or considered to require radiation therapy during the study;

14. Female patients who are pregnant or breast feeding;

15. Female patients of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards;

16. Treatment with any other investigational agent within the 4 months prior to study entry;

17. For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Kyowa Kirin Co., Ltd.

Locations

Tokyo, , Japan

Countries

Japan

References

Ishida T, Ueda R. CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci. 2006 Nov;97(11):1139-46. doi: 10.1111/j.1349-7006.2006.00307.x. Epub 2006 Sep 5.

Reference Type: BACKGROUND

PMID: 16952304 (View on PubMed)

Yano H, Ishida T, Inagaki A, Ishii T, Ding J, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R. Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome. Clin Cancer Res. 2007 Nov 1;13(21):6494-500. doi: 10.1158/1078-0432.CCR-07-1324.

Reference Type: BACKGROUND

PMID: 17975162 (View on PubMed)

Yano H, Ishida T, Inagaki A, Ishii T, Kusumoto S, Komatsu H, Iida S, Utsunomiya A, Ueda R. Regulatory T-cell function of adult T-cell leukemia/lymphoma cells. Int J Cancer. 2007 May 1;120(9):2052-7. doi: 10.1002/ijc.22536.

Reference Type: BACKGROUND

PMID: 17278106 (View on PubMed)

Other Identifiers

0761-0501

Identifier Type: -

Identifier Source: org_study_id