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

October 17, 2012 updated by: Kyowa Kirin Co., Ltd.

Phase I Dose Escalation Study of KW-0761 in Patients With Relapsed Adult T-Cell Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 69 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1
KW-0761
Drug: KW-0761
IV administration at 4 escalating dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame: 28 days
Subjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.
28 days
Maximum Tolerated Dose (MTD)
Time Frame: 28 days
The dose level at which Dose-Limiting Toxicity (DLT) was recognized was to be regarded as Maximum Tolerated Dose (MTD), and the dose level below MTD by one level was to be regarded as the recommended dose level (when MTD was not reached, 1.0 mg/kg was to be regarded as the recommended dose level) and 3 more subjects were to be newly added to the recommended dose level.
28 days
Pharmacokinetics-Plasma KW-0761 Concentrations
Time Frame: 0-7 days post final dose
Plasma KW-0761 concentrations were to be summarized in tabular form with the descriptive statistics on a dose-by-dose basis. Individual and mean (+ standard deviation) plasma KW-0761 concentrations on an actual or logarithmic scale were to be plotted against the time of blood sampling.
0-7 days post final dose
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days)
Time Frame: 0-7 days post final dose
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
0-7 days post final dose
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2)
Time Frame: 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).
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antitumor Effect
Time Frame: 50 days
The antitumor response criteria (Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) were created based on the criteria for non-Hodgkin's lymphoma and chronic lymphocytic leukemia provided in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as well as the criteria for non-Hodgkin's lymphoma by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG).
50 days
Time to Progression (TTP)
Time Frame: Baseline to response
TTP was defined as the period from the day starting the first KW-0761 dosing to the day of PD identification (or the day of death if the subject died before PD was documented). Subjects were to be censored at the time of starting post-treatment, if it was started before PD identification.
Baseline to response

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kyowa Kirin Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2007

Primary Completion (ACTUAL)

October 1, 2008

Study Completion (ACTUAL)

October 1, 2008

Study Registration Dates

First Submitted

July 20, 2006

First Submitted That Met QC Criteria

July 20, 2006

First Posted (ESTIMATE)

July 24, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

October 18, 2012

Last Update Submitted That Met QC Criteria

October 17, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0761-0501

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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