Efficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia

Inclusion criteria

Patients meeting all of the following criteria are to be included in the study:

• Patients aged between 20 and 80 years (at the time of registration)
• Patients who have provided written consent in person for participation in this study
• Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
• Patients who are expected to survive for at least 3 months
• Patients who are naive to or not suitable for fludarabine therapy
• Patients who are documented with chronic lymphocytic leukemia on the basis of International Workshop on Chronic Lymphocytic Leukaemia guideline (IWCLL) guideline:

• The presence of ≥ 5000/mm3 monoclonal mature B-lymphocytes in the peripheral blood
• ≤ 55 % atypical lymphocytes, prolymphocyte-like cells, and lymphoblasts with prominent nucleoli
• For monoclonal mature B-lymphocytes, at least one of the B-cell specific differentiation antigens (Cluster of differentiation (CD) 19, CD 20, and CD 23) and CD 5 is positive by flow cytometry
• Patients in Stage C or stage B with active disease based on Binet staging system (at the time of registration)

• Decision to start treatment should be made upon IWCLL guideline criteria.
• Active disease is defined to meet at least one of the following criteria.

• Progression and/or worsening of anemia and/or thrombocytopenia caused by decreased bone marrow function.
• Massive (6 cm below the left costal margin) or progressive or symptomatic splenomegaly
• Massive nodes (≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
• Progressive lymphocytosis with an increase of > 50% over a 2-month period, or lymphocyte doubling time of less than 6 months
• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
• B symptoms Weight loss > 10% within the previous 6 months Fevers of greater than 38.0° C for 2 or more weeks without other evidence of infection Night sweats
• Patients with 2 or less regimens of previous chemotherapy including antibody therapy. Corticosteroid monotherapy is not counted.
• Patients with adequately maintained organ functions (e.g., bone marrow, heart, lung, liver, and kidney functions)

• Neutrophil count: ≥ 1,000 /mm3
• Aspartate aminotransferase(AST) Glutamic oxaloacetic transaminase(GOT): ≤ 3.0 times the upper limit of normal range at each site
• Alanine aminotransferase (ALT) Glutamic pyruvic transaminase(GPT): ≤ 3.0 times the upper limit of normal range at each site
• Total bilirubin: ≤ 1.5 times the upper limit of normal range at each site
• Serum creatinine: ≤ 1.5 times the upper limit of normal range at each site
• Partial pressure of O2 (PaO2): ≥ 65 mmHg
• No abnormalities which require treatment are detected on ECG
• Left ventricular ejection fraction (LVEF) (echocardiography): ≥ 55%

Exclusion criteria

Patients who fall under any one of the following criteria are to be excluded

• Patients who have been without treatment for less than 4 weeks after prior treatment. For patients treated with antibody therapy or underwent hematopoietic stem cell transplantation, for 3 months after prior treatment
• Patients who enrolled other clinical studies within 4 weeks before registration for this study
• Patients who received allogeneic stem cell transplantation in the past
• Patients with defective p53 (17p-) confirmed by chromosome analysis (Fluorescence in situ hybridization (Fish) method)
• Patients who are clinically diagnosed with Richter's syndrome
• Patients with infiltration to the central nervous system (CNS) or patients with clinical symptoms of suspected infiltration to the CNS
• Patients with multiple primary cancers or patients with a history of other malignant tumors within past 5 years, except for basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or gastrointestinal tract
• Patients with serious bleeding tendencies (e.g., disseminated intravascular coagulation (DIC))
• Patients with, or confirmed in the past to have had, interstitial lung disease or pulmonary fibrosis
• Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia responds to corticosteroid therapy
• Patients with any of the following complications

• serious cardiac disease (e.g., myocardial infarction, ischemic heart disease, or arrhythmia requiring treatment)
• serious, active infections (requiring intravenous administration of antibiotics, antifungal drugs, or antiviral drugs)
• hepatic or renal dysfunction
• accumulation of pleural effusion, pericardial effusion, or peritoneal effusion
• uncontrollable serious gastrointestinal disease, endocrine disorder, or mental illness
• Patients who received SyB L-0501 in the past
• Patients with allergies to mannitol
• Patients who need cytokine preparations such as erythropoietin or granulocyte colony stimulating factor (G-CSF) or blood transfusions at registration for this study
• Patients positive for HIV antibody or Hepatitis C virus (HCV) antibody
• Patients positive for Hepatitis B surface (HBs) antigen. Patients with negative results will also be checked for Hepatitis B core (HBc) antibody and HBs antibody. If either of the test results is positive, measure Hepatitis B virus (HBV)-DNA and exclude the patients with results above sensitivity
• Patients with clinical symptom of cytomegalovirus (CMV) infection, except asymptomatic patients with CMV positive
• Patients who are pregnant, who may possibly be pregnant, or lactating
• Patients who do not agree to practice contraception. Male: During investigational product administration and until 6 months after final administration Female: During investigational product administration and until 4 months after final administration
• Patients with drug addiction, narcotics addiction, and/or alcohol dependency
• Patients otherwise judged by the investigator or sub-investigator to be unsuitable for inclusion in this study