A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphomaperipheral T-cell Lymphoma

Inclusion Criteria:

1. Subject must understand and voluntarily sign the written informed consent;
2. Aged 20 years or older;

3. Subject have a documented diagnosis of either:

   • Acute-, lymphoma-, or unfavorable chronic-type ATL or
   • Peripheral T-cell Lymphomaperipheral (PTCL)
4. Subject have received ≥1 prior anti-cancer therapy, have achieved stable disease (SD) or better on their immediately prior therapy and have relapsed or progressed at the time of obtaining signed informed consent;
5. Subject have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2 at enrollment;

Exclusion Criteria:

1. Natural Killer cell lymphoma (NK-cell lymphoma);
2. T-cell leukemia;

3. Cutaneous T-cell lymphoma (CTCL) including;

   • Mycosis fungoides
   • Sezary syndrome
   • CD30-positive lympho-proliferative disorders
   • Cutaneous gamma/delta T-cell lymphoma
4. Subject have a history of central nervous system (CNS) involvement or present with CNS symptoms, and are diagnosed with CNS lymphoma by cerebrospinal fluid (CSF) cytology examination, head CT scan or brain MRI during the screening;
5. Are pregnant or lactating;

6. Subject have uncontrolled inter-current illness including:

   • Uncontrolled diabetes mellitus
   • Chronic congestive heart failure (NYHA Class III or IV)
   • Unstable angina pectoris, angioplasty, stenting, or myocardial infarction (within 6 months before starting the study drug)
   • Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia
   • Other uncontrolled diseases
7. Exhibit grade 4 neurological disorders;
8. Subject have a history or complication of deep vein thrombosis or pulmonary embolism within 6 months before the start of study treatment;
9. Develop active tuberculous disease, herpes simplex, systemic mycosis, or other active infections requiring systemic administration of antibiotics, antiviral agents, or antifungal drugs;
10. Are tested positive for HBs antigen, anti-HCV antibody, or anti-HIV antibody;
11. Subjects have a history or complication for which the investigator or subinvestigator deems them inappropriate for this study, or have serious diseases or mental illness that is likely to be aggravated by participation in this study;
12. Subjects have a history of allogeneic stem cell transplantation;
13. Subjects have received autologous stem cell transplantation within 12 weeks (84 days) of the start of study treatment;
14. Have previously used lenalidomide;
15. Have a history of desquamating (bullous) rash while taking thalidomide;
16. Have received any investigational drugs (unapproved drugs in Japan) within 4 weeks (28 days) of the start of study medication;
17. Have received chemotherapeutic agents or immunomodulators for the treatment of ATL or PTCL within 4 weeks (28 days) of the start of study treatment;
18. Have received radiotherapy within 4 weeks (28 days) of the start of study treatment;

19. Have a history or complication of another malignant tumor than ATL or PTCL (excluding malignant tumors below), unless the patients have been free of the disease for 5 years or longer;

    • Cutaneous basal cell carcinoma or squamous cell carcinoma
    • Cervical carcinoma in situ
    • An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b)

20. Have had any of the following abnormal measurements at screening performed within 1 week (7 days) prior to the enrollment;

    • Neutrophil count: < 1,200/µL (1.2 x 109/L)
    • Platelet count: < 75,000/µL (75 x 109/L)
    • Serum aspartate aminotransferase/ Serum glutamic oxaloacetic transaminase (AST/SGOT) or Alanine transaminase/Serum Glutamic Pyruvate Transaminase (ALT/SGPT): > 3 times the Upper Limit of Normal (ULN)
    • Bilirubin level: > 1.5 times of the ULN
    • Creatinine clearance: < 60 mL/min