About this trial
This phase II trial tests how well zanubrutinib and lisocabtagene maraleucel (liso-cel) work together in treating patients with Richter's syndrome that has come back (recurrent) or does not respond to treatment (refractory). Richter's syndrome occurs when chronic lymphocytic leukemia and/or small lymphocytic leukemia transforms into an aggressive lymphoma, which is a cancer of the lymph nodes. Zanubrutinib is a class of medication called a kinase inhibitor. These drugs work by preventing the action of abnormal proteins that tell cancer cells to multiply, which helps stop the spread of cancer. Liso-cel is a type of treatment known as chimeric antigen receptor (CAR) T cell therapy. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving zanubrutinib and liso-cell together may kill more cancer cells in patients with recurrent or refractory Richter's syndrome.
Eligibility criteria
Qualifiers
Diagnosis of RS - occurrence of diffuse large B-cell lymphoma (DLBCL) in patients with antecedent or concurrent CLL/SLL (CLL/SLL diagnosis per IWCLL 2018 criteria).
Participants must have undergone >= 1 prior systemic therapeutic regimen administered for >= 1 cycle for either CLL or RS, and have had either documented disease progression to the most recent treatment regimen, or refractory disease. OR
Developed RS while receiving treatment for CLL
Age >= 18 years
Disqualifiers
A history of treatment including any of the following: prior CD19 directed therapy, treatment with alemtuzumab within 6 months before enrollment, prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 2 months prior to enrollment
Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
Inadequate recovery from adverse events related to prior therapy to grade =< 1 (excluding grade 2 alopecia, neuropathy, and hypertension)
Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
Trial design
Treatments tested in this trial
- Biospecimen Collection
- Bone Marrow Biopsy
- Computed Tomography
- Cyclophosphamide
- Fludarabine
- Leukapheresis
- Lisocabtagene Maraleucel
- Lymph Node Biopsy
- Positron Emission Tomography
- Zanubrutinib
Treatment groups
Sponsors and collaborators
Aseel Alsouqi
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
BeOne Medicines
Collaborator