B001 in Patients With CD20 Positive B-cell Non Hodgkin's Lymphoma

Phase I dose escalation study

Inclusion criteria

• Age of 18-75, male or female.
• Patients with the following histologically-documented hematologic malignancy: CD20 positive B-cell non Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to 2016 WHO Classification of Lymphoma.
• Patients with relapsed/refractory CD20 positive B cell NHL (including CLL/SLL )
• Life expectancy of at least 6 months.
• ECOG-PS score of 0-1.
• For patients of reproductive potential, pregnancy test should be negative 7 days before treatment , and use of a reliable means of contraception during the study and 12months after discontinuing treatment. Males should be willing to use barrier contraception during the study and 12months after discontinuing treatment.
• Provision of signed and dated ,written informed consent prior to any study specific procedures, sampling and analyses.

Exclusion criteria

• Serious blood, renal or hepatic function impairment:

• Absolute neutrophil count(ANC)<1.0*10^9/L（Except for those with bone marrow invasion）
• Lymphocyte Count(LYM)>50*10^9/L
• Haemoglobin(Hb)<70g/L（Except for those with bone marrow invasion）
• Platelet count(PLT)<50*10^9/L（Except for those with bone marrow invasion）
• Creatinine (Cr)>1.5xULN
• Alanine transaminase (ALT)or Aspartate aminotransferase(AST)>2.5xULN
• Total bilirubin (TBIL)>2xULN
• Patients with any anti-tumor treatment (including steroid treatment) within 4 weeks or with any chronic unresolved toxicities from prior therapy greater than Grade 2 according to NCI-CTCAE 4.03.
• Rituximab or any other anti-CD20 monoclonal antibody treatment within 3 weeks.
• received blood transfusion and hemopoietic stimulating factor,eg. colony-stimulating factor (CSF)、Erythropoietin(EPO) within 2 weeks.
• Radiotherapy within 3 months.
• Major surgery within 28 days
• History of tumor vaccine treatment.
• Live-virus (live attenuated) vaccine treatment within 28 days
• High dose of steroid treatment (hydroprednisone >10mg/day or relevant dose of other drugs)
• Patients with history of hematopoietic stem cell transplantation or planning to receive hematopoietic stem cell transplantation within 3 months.
• Patients with history of Gastrointestinal perforation and/or fistula within 6 months.
• Lymphoma in CNS, ADIS related lymphoma
• Active infection by bacteria,virus,fungus which required hospitalization or severe infection required intravenous administration of antibiotics
• Concomitant severe disease including but not limited to:

• Known HIV or ADIS related disease
• Asthma or interstitial lung disease or severe COPD
• Myocardial infarction, unstable angina, Cardiovascular interventional surgery, Congestive heart failure(CHF; NYHA Grade II-IV), symptomatic or poorly controlled arrhythmia within 6 months before enrolling
• The systolic pressure ≥140mmHg,or diastolic pressure≥90mmHg post treatment.
• Acute or chronic hypotension(<90/60mmHg)
• History of toxic epidermal necrolysis or Stevens-Johnson syndrome
• Rheumatoid arthritis Granulomatous angiitis or microscopic polyangiitis
• Ileus or history of following disease: inflammatory bowel disease or extensive intestinal resection(extensive bowel resection or hemicolectomy, combining chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea.
• Previous or concomitant malignant, except basal-cell carcinoma or squamous cell carcinoma and/or cervical carcinoma in situ or effectively treated hematological malignancy and solid tumor that has been remission for more than 3 years and is considered to be cured.
• Any history may affect the study result: increasing dosing risk or affect lab values and Judgment by the investigator that the patient should not participate in the study,
• HBsAg positive; HBcAb positive and HBV-DNA≥upper limit of detection, HCV positive; HIV positive
• Allergy to humanized antibody or human-mouse chimeric antibody.
• Woman who are breast feeding or pregnant
• Judgment by the investigator that the patient should not participate in the study