Phase 2 Study of the Combination of Lisocabtagene Maraleucel, Nivolumab, and Ibrutinib in Richter's Transformation
This phase II trial tests how well adding lisocabtagene maraleucel (liso-cel) to nivolumab and ibrutinib works in treating patients with Richter's transformation. Liso-cel is in a class of medications called autologous cellular immunotherapy, a type of medication prepared by using cells from patient's own blood. It works by causing the body's immune system (a group of cells, tissues, and organs that protects the body from attack by bacteria, viruses, cancer cells and other substances that cause disease) to fight the cancer cells. Nivolumab is in a class of medications called monoclonal antibodies. It works by helping the immune system to slow or stop the grown of cancer. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Giving ibrutinib and nivolumab with Liso-cel may kill more cancer cells in patients with Richter's transformation.
• Documented informed consent of the participant
• Agreement for confirmatory pre-treatment tumor biopsy
‣ If a patient does not have an easily accessible lymph node to biopsy without excessive risk in the opinion of the investigator, archival biopsy material reviewed by a hematopathologist at the enrolling site for study eligibility and baseline correlatives may be acceptable with approval from the Study principal investigator (PI)
• Age: \>= 18 years
• Eastern cooperative oncology group (ECOG) \<= 2
• Histologically confirmed Richter's Transformation (RT)
• Relapsed / refractory following \>=2 prior lines of systemic therapy; OR refractory to first-line chemoimmunotherapy; OR relapsed within 12 months of first line chemoimmunotherapy; OR relapsed after first line of chemoimmunotherapy and not eligible for hematopoietic stem cell transplantation due to comorbidities or age
• Eligible to receive liso-cel and ibrutinib per package inserts
• Fully recovered from the acute toxic effects (except alopecia) to \<= Grade 1 to prior anti-cancer therapy
• Absolute neutrophil count (ANC) \>= 750/mm\^3 unless there is bone marrow involvement
• Platelets \>= 75,000/mm\^3 unless there is bone marrow involvement
• Total bilirubin =\< 1.5 X ULN (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) =\< 2.5 x ULN
• Alanine aminotransferase (ALT) =\< 2.5 x ULN
• Creatinine clearance of \>= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• International Normalized Ratio (INR) OR Prothrombin (PT) =\< 1.5 x ULN
• Activated Partial Thromboplastin Time (aPTT) =\< 1.5 x ULN
• Left ventricular ejection fraction (LVEF) \>= 40%
‣ Note: To be performed within 28 days prior to Day 1 of protocol therapy.
• Seronegative for HCV\*, active HBV (Surface Antigen Negative), and syphilis (RPR)
‣ If positive, Hepatitis C RNA quantitation must be performed OR
⁃ If seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
• Meets other institutional and federal requirements for infectious disease titer requirements
‣ Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
‣ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months after the last dose of protocol therapy
‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)