Cirmtuzumab and Venetoclax as Consolidation Therapy for the Treatment of Patients with Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia Previously Treated with Venetoclax

Inclusion Criteria

• Both men and women of all races and ethnic groups are eligible for this trial
• Ability to understand and willingness to sign a written informed consent
• CLL or SLL, as documented in the medical record
• Must have detectable CLL (> 0.01% CLL cells in the blood or marrow)
• Must have received at least 12 months of venetoclax
• Patients may be receiving venetoclax at the time of screening and study entry
• Patients who have discontinued venetoclax more than 6 months prior to study entry must still have a disease burden meeting criteria for low risk of tumor lysis syndrome (TLS) (i.e. no lymph node greater than 5 cm in diameter; absolute lymphocyte count less than 25 k/uL)
• Has recovered from the toxic effects of prior therapy to their clinical baseline
• Women of child-bearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree to not become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 5 half-lives after the final dose of venetoclax (approximately 1 week), and at least 5 half-lives of final dose of cirmtuzumab (approximately 5 months)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Platelet count >= 30 k/uL
• Hemoglobin > 7 g/dL
• Absolute neutrophil count (ANC) > 500/uL
• Creatinine clearance based on 24 hour (hr) collection >= 40 ml/min; OR calculated creatinine clearance (CrCl) >= 40 mL/min (based upon the Cockcroft-Gault equation)
• Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0 x ULN
• Bilirubin =< 1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)

Exclusion Criteria

• Subject is known to be positive for human immunodeficiency virus (HIV) (HIV testing is not required.)
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: * Uncontrolled and/or active systemic infection (viral, bacterial or fungal) * Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface [HBs] antigen negative, anti-HBs antibody positive and anti-hepatitis B core [HBc] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate * Child class B or C cirrhosis
• Treatment with any of the following within 7 days prior to the first dose of cirmtuzumab: * Steroid therapy for anti-neoplastic intent * Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent * Chemotherapy (purine analog or alkylating agent) or target small molecule agent within 14 days or 5 half-lives (whichever is shorter), or has not recovered to less than circulating tumor cell (CTC) grade 2 clinically significant adverse effect(s)/toxicity(s) of previous therapy * CLL therapy, aside from venetoclax
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs
• History of other malignancy that could affect compliance with the protocol or interpretation of results (example: patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible)
• Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds); or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of cycle 1
• Major surgery (within 4 weeks prior to the start of cycle 1), other than for diagnosis
• Women who are pregnant or lactating
• Myocardial infarction within 6 months of starting study drug or other clinically significant heart disease (New York Heart Association [NYHA] class 3 heart failure, uncontrolled hypertension)