Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL
Condition: Adult T-Cell Leukemia and Lymphoma (ATL); Adult Peripheral T-Cell Lymphoma (PTCL)
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
Intervention: KW-0761
Intervention description: IV administration at 4 escalating dose levels.
Intervention MeSH terms: Mogamulizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 20 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Adult T-Cell Leukemia; ATL; Adult Peripheral T-Cell Lymphoma; PTCL

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).
    

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.