Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation

Inclusion Criteria

• •Subject must have confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) based upon 2018 International Workshop on CLL (IwCLL) criteria, with biopsy proven Richter's Transformation to a DLBCL subtype.
• •Subject must be ≥18 years of age.
• •Subject must be able to sign informed consent
• •Ability and willingness to comply with the study protocol procedures
• •Life expectancy of at least 24 weeks
• •Subject must have an Eastern Cooperative Oncology Group performance status of ≤2.
• •Subject must have measurable disease with atleast on LN\>- 1.5cm in longest diameter
• •Subject must have adequate bone marrow function and meet the below thresholds prior to treatment.
• •* Absolute neutrophil count of ≥1000 cell/uL
• •* Hemoglobin ≥ 7 g/dL
• •* Platelet count ≥ 30,000 cells/uL- Subjects may receive growth factor or transfusion support no less than 7 days prior to enrollment or C1 D1.
• •Subject must have adequate organ function and meet the thresholds below:
• •* Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's disease will be granted exception to this rule.
• •* Creatinine clearance \>30 ml/min/1.73m2 as calculated by the MDRD equation.
• •* Ejection fraction ≥ 50% measured by transthoracic echocardiogram or MUGA scan
• •For women of childbearing potential: agreement to remain abstinent or use of contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 12 months after the last dose of study drug.
• •* A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (i.e. ≥ 12 months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (removal of ovaries and or uterus)
• •* Acceptable forms of contraception are bilateral tubal ligation, male sterilization, or copper intrauterine devices.
• •* For women considered to have childbearing potential a negative serum pregnancy test within 7 days prior to study enrollment and dosing is required.
• •For men, agreement to remain abstinent, or to use a condom plus an additional contraceptive method during the treatment period and for at least 5 months after the last dose of study drug.
• •* Men must agree not to donate sperm during that period of time. Male patients interested in preservation of fertility should be advised to sperm bank prior to enrollment and treatment initiation.
• •Subject is known to be positive for HIV.
• •Active hepatitis C or hepatitis B defined by positive PCRs for viral DNA/RNA. Subjects with a positive Hep B core antibody and negative PCR, are allowed to enroll (prophylaxis is strongly encouraged and monthly monitoring of Hep B PCR is mandatory).
• •Subject has baseline ≥ Grade 2 or greater peripheral neuropathy.
• •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• •Clinical evidence or known central nervous system involvement with transformed large cells
• •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• •Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina)
• •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks before Cycle 1 day 1.
• •Major surgery within 4 weeks before the start of Cycle 1 day 1. Superficial lymph node biopsies or laprascopic lymph node biopsies are exclusionary to this rule.