A Randomized Phase III Study of Pirtobrutinib Plus R-CHOP vs. R-CHOP for Participants With Previously Untreated Richter Transformation (PIRAMID)
SWOG Cancer Research Network
Summary
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.
Description
PRIMARY OBJECTIVES: I. In participants aged 74 and younger, to evaluate the safety of the addition of pirtobrutinib to R-CHOP before initiating randomization in participants with untreated Richter Transformation to large B-cell lymphoma (LBCL). (Safety run-in) II. In participants aged 75 and older, to evaluate the safety of the addition of pirtobrutinib to R-mini-CHOP before initiating randomization in this patient population. (Safety run-in) III. To evaluate whether the addition of pirtobrutinib to R-CHOP improves investigator-assessed progression-free survival (PFS) compared to R-CHOP alone…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 * Participants are allowed prior treatments for CLL/SLL or its complications (autoimmune hemolytic anemia \[AIHA\], immun…
Interventions
- ProcedureBiospecimen Collection
Undergo blood and buccal swab sample collection
- ProcedureComputed Tomography
Undergo CT scan and/or PET/CT scan
- DrugCyclophosphamide
Given IV
- DrugDoxorubicin Hydrochloride
Given IV
- ProcedureEchocardiography Test
Undergo echocardiography
- ProcedureMultigated Acquisition Scan
Undergo MUGA scan
- DrugPirtobrutinib
Given PO
- ProcedurePositron Emission Tomography
Undergo PET/CT scan
- DrugPrednisone
Given PO
- BiologicalRituximab
Given IV
- BiologicalRituximab and Hyaluronidase Human
Given SC
- OtherSurvey Administration
Ancillary studies
- DrugVincristine
Given IV
Locations (62)
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UCI Health Laguna HillsLaguna Hills, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- Illinois CancerCare-BloomingtonBloomington, Illinois
- Illinois CancerCare-CantonCanton, Illinois
- Illinois CancerCare-CarthageCarthage, Illinois