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RECRUITING Phase 3 ClinicalTrials.gov

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

Sponsor: SWOG Cancer Research Network • ClinicalTrials.gov ID: NCT07220187

Registry updated: 2026-10-13
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Description

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.

Interventions

  • Biospecimen Collection (Procedure)
    Undergo blood and buccal swab sample collection
  • Computed Tomography (Procedure)
    Undergo CT scan and/or PET/CT scan
  • Cyclophosphamide (Drug)
    Given IV
  • Doxorubicin Hydrochloride (Drug)
    Given IV
  • Echocardiography Test (Procedure)
    Undergo echocardiography
  • Multigated Acquisition Scan (Procedure)
    Undergo MUGA scan
  • Pirtobrutinib (Drug)
    Given PO
  • Positron Emission Tomography (Procedure)
    Undergo PET/CT scan
  • Prednisone (Drug)
    Given PO
  • Rituximab (Biological)
    Given IV
  • Rituximab and Hyaluronidase Human (Biological)
    Given SC
  • Survey Administration (Other)
    Ancillary studies
  • Vincristine (Drug)
    Given IV

Eligibility criteria

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 \[AIHA\], 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 * Participants must not have a prior or concurrent malignancy in addition to CLL/SLL and Richter transformation whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen * Participants must not have had major surgery within 28 days prior to registration * Participants must not have experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. * NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome * Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen * Participants must be offered the opportunity to participate in specimen banking * Participants must agree to have blood and lymphatic tissue specimens submitted for the integrated translational medicine study * For randomized participants only: Participants who can complete PRO-CTCAE and FACIT GP5 questionnaires forms in English or Spanish must be offered the opportunity to participate in the patient-reported outcome

Conditions

Richter Syndrome Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma

Locations

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States
  • UCI Health Laguna Hills — Laguna Hills, California, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
  • Illinois CancerCare-Bloomington — Bloomington, Illinois, United States
  • Illinois CancerCare-Canton — Canton, Illinois, United States
  • Illinois CancerCare-Carthage — Carthage, Illinois, United States
  • Carle at The Riverfront — Danville, Illinois, United States
  • Cancer Care Specialists of Illinois - Decatur — Decatur, Illinois, United States
  • Decatur Memorial Hospital — Decatur, Illinois, United States
  • Carle Physician Group-Effingham — Effingham, Illinois, United States
  • Illinois CancerCare-Eureka — Eureka, Illinois, United States
  • Illinois CancerCare-Galesburg — Galesburg, Illinois, United States
  • Illinois CancerCare-Kewanee Clinic — Kewanee, Illinois, United States
  • Illinois CancerCare-Macomb — Macomb, Illinois, United States
  • Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States
  • Carle BroMenn Medical Center — Normal, Illinois, United States
  • Carle Cancer Institute Normal — Normal, Illinois, United States
  • Cancer Care Center of O'Fallon — O'Fallon, Illinois, United States
  • HSHS Saint Elizabeth's Hospital — O'Fallon, Illinois, United States
  • Illinois CancerCare-Ottawa Clinic — Ottawa, Illinois, United States
  • Illinois CancerCare-Pekin — Pekin, Illinois, United States
  • Illinois CancerCare-Peoria — Peoria, Illinois, United States
  • Illinois CancerCare-Peru — Peru, Illinois, United States
  • Illinois CancerCare-Princeton — Princeton, Illinois, United States
  • Memorial Hospital East — Shiloh, Illinois, United States
  • Southern Illinois University School of Medicine — Springfield, Illinois, United States
  • Springfield Clinic — Springfield, Illinois, United States
  • Springfield Memorial Hospital — Springfield, Illinois, United States
  • Carle Cancer Center — Urbana, Illinois, United States
  • Illinois CancerCare - Washington — Washington, Illinois, United States
  • Our Lady of the Lake Physician Group — Baton Rouge, Louisiana, United States
  • Trinity Health IHA Medical Group Hematology Oncology - Brighton — Brighton, Michigan, United States
  • Trinity Health IHA Medical Group Hematology Oncology - Canton — Canton, Michigan, United States
  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital — Chelsea, Michigan, United States
  • Trinity Health Saint Mary Mercy Livonia Hospital — Livonia, Michigan, United States
  • Trinity Health Saint Joseph Mercy Oakland Hospital — Pontiac, Michigan, United States
  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus — Ypsilanti, Michigan, United States
  • Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
  • Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
  • Washington University School of Medicine — St Louis, Missouri, United States
  • Siteman Cancer Center-South County — St Louis, Missouri, United States
  • Siteman Cancer Center at Christian Hospital — St Louis, Missouri, United States
  • UNC Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
  • Duke University Medical Center — Durham, North Carolina, United States
  • Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
  • Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States
  • VCU Massey Cancer Center at Stony Point — Richmond, Virginia, United States
  • VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
  • FHCC Overlake — Bellevue, Washington, United States
  • FHCC at EvergreenHealth — Kirkland, Washington, United States
  • Fred Hutchinson Cancer Center — Seattle, Washington, United States
  • FHCC at Northwest Hospital — Seattle, Washington, United States
  • University of Washington Medical Center - Montlake — Seattle, Washington, United States
  • Froedtert Menomonee Falls Hospital — Menomonee Falls, Wisconsin, United States
  • Medical College of Wisconsin — Milwaukee, Wisconsin, United States
  • ProHealth D N Greenwald Center — Mukwonago, Wisconsin, United States
  • Froedtert and MCW Moorland Reserve Health Center — New Berlin, Wisconsin, United States
  • Drexel Town Square Health Center — Oak Creek, Wisconsin, United States
  • ProHealth Oconomowoc Memorial Hospital — Oconomowoc, Wisconsin, United States
  • ProHealth Waukesha Memorial Hospital — Waukesha, Wisconsin, United States
  • UW Cancer Center at ProHealth Care — Waukesha, Wisconsin, United States
  • Froedtert West Bend Hospital/Kraemer Cancer Center — West Bend, Wisconsin, United States
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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

View Official Record