Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial

Starting soon · Phase 3

Conditions studied: Richter Syndrome, Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma, Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma

In brief

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.

Key facts

Study ID: NCT07220187
Run by: SWOG Cancer Research Network
People needed: 102
Starts: 2026-08-31
Expected to finish: 2036-10-01
Last updated by the study team: 2026-06-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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], immune thrombocytopenic purpura [ITP]), with the exception of pirtobrutinib
Participants must not have prior treatment for Richter transformation except for corticosteroids up to equivalent dose of prednisone 700 mg total for less than 7 days for disease control. Treatment for CLL/SLL with CLL/SLL directed drugs (including BTK inhibitors with the exception of pirtobrutinib) after the Richter transformation diagnosis is allowed for the purpose of disease control. CLL targeted therapies must be stopped within 3 days before initiation of therapy on protocol. Chemotherapy or anti-CD20 monoclonal antibody therapy must be stopped within 2 weeks before initiation of therapy on protocol
Participants must not have contraindication for receiving anthracycline. Participants must not have received more than a cumulative dose of 100mg/m\^2 in those participants who will receive R-CHOP or not more than 250 mg/m\^2 in those participants who will receive R-mini-CHOP of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration)
Patients requiring strong CYP3A inducers are not eligible and can only be enrolled if
an alternative treatment to the strong CYP3A inducer is available for them and
the last dose of the strong CYP3A inducer is administered at least 7 days before initiation of pirtobrutinib for patients in safety run-in and arm 1
Participant must be ≥ 18 years old at the time of registration
Participant must have Eastern Cooperative Oncology Group (ECOG)/Zubrod Performance Status of 0-2
Participant must have a complete medical history and physical exam within 28 days prior to registration
Absolute neutrophil count (ANC) ≥ 0.75 x 10\^3/µL or ≥ 0.50 x 10\^3/µL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
Platelets ≥ 50 x 10\^3/µL or ≥ 30 x 10\^3/µL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
Hemoglobin ≥ 8 g/dL (≥ 80 g/L) or ≥ 6 g/dL in participants with suspected bone marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or ≤ 3 x ULN with documented liver involvement and/or Gilbert's disease (within 28 days prior to registration)
Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 × institutional ULN or ≤ 5 ULN with documented liver involvement (within 28 days prior to registration)
Participants must have a calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration. For the Cockcroft-Gault formula for calculated creatinine clearance, see the tools on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx
Participants must have a left ventricular ejection fraction (LVEF) ≥ 45% as measured by echocardiogram or radionuclide (MUGA) ventriculography within 56 days prior to registration
Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Participants' HIV-directed therapy cannot have known interactions with pirtobrutinib
Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration
Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration
Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications

Full record on ClinicalTrials.gov

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