Clinical trial NCT00355472: Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL
Official title: Phase I Dose Escalation Study of KW-0761 in Patients With Relapsed Adult T-Cell Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2006-07-24
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD)
timeFrame: 28 days
measure: Pharmacokinetics-Plasma KW-0761 Concentrations
timeFrame: 0-7 days post final dose
measure: Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days)
timeFrame: 0-7 days post final dose
measure: Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2)
timeFrame: 0 to 28 days post final dose and follow-up examinations (1 month and 2 months after the end of the post-dosing observation period).
Secondary outcomes:
measure: Antitumor Effect
timeFrame: 50 days
measure: Time to Progression (TTP)
timeFrame: Baseline to response
Other outcomes:
Locations:
city: Tokyo
country: Japan
Study officials:
affiliation: Kyowa Kirin Co., Ltd.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.