This phase III trial compares the effect of adding pirtobrutinib to the usual treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) to R-CHOP alone for the treatment of Richter transformation, which is when chronic lymphocytic leukemia or small lymphocytic lymphoma turns into large B-cell lymphoma, a more aggressive (faster-growing) form of lymphoma. Pirtobrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Adding pirtobrutinib to R-CHOP may kill more cancer cells than R-CHOP alone in patients with Richter transformation.
Participants must have been diagnosed with Richter Transformation (RT) (CLL/small lymphocytic lymphoma [SLL] to LBCL)
Participants must have histologically or cytologically confirmed LBCL
Participants must have measurable disease determined by PET/CT or hematopathology (by morphology or flow cytometry) assessment within 42 days prior to registration
Participants must have staging PET/CT imaging performed within 42 days prior to registration
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood and buccal swab sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan and/or PET/CT scan
Cyclophosphamide
DrugGiven IV
Doxorubicin Hydrochloride
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo echocardiography
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA scan
Pirtobrutinib
DrugGiven PO
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT scan
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Rituximab and Hyaluronidase Human
Biological/VaccineGiven SC
Survey Administration
Other interventionAncillary studies
Vincristine
DrugGiven IV
Progression free survival (PFS)
Progression free survival: is measured from date of randomization to the first of progression or death from any cause. Participants last known to be alive without progression will be censored at the date of last contact.
Overall free survival
Overall free survival: is measured from date of randomization date of death from any cause. Participants last known to be alive will be censored at the date of last contact.
Overall Response
Will estimate outcomes (CR, ORR, MRD) for each arm as proportions with binomial confidence intervals. Proportions will be compared between arms using Fisher's exact test.
Complete Remission
Complete disappearance of all measurable and non-measurable disease.
Incidence of adverse events
Number of patients with grade 3 through 5 adverse events that are related (possibly, probably, definitely) to protocol therapy
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SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
