Phase II Study of Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation
This study evaluates the effectiveness and safety of Polatuzumab vedotin plus infusional chemoimmunotherapy containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin. This is a single arm study. Enrolled patients will receive up to six cycles (21-day cycles) of therapy. While on study, subjects will be monitored weekly until end of treatment, then followed for 52 weeks or until disease progression or discontinuation due to toxicity or death. After completion of the 52-week follow-up/End of study visit, Subjects will be followed for an additional 104 week period, with an assessment occurring every 12 weeks to evaluate survival outcomes and next line of treatments only.
• 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.