NCT07220187RecruitingPhase 3
Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial
A Randomized Phase III Study of Pirtobrutinib Plus R-CHOP vs. R-CHOP for Participants With Previously Untreated Richter Transformation (PIRAMID)
Source: ClinicalTrials.gov · Last updated 13 Oct 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 3
- Study type
- Interventional
- Enrollment
- 102 (estimated)
- First submitted
- 6 Oct 2025
- Start date
- 4 Aug 2026
- Primary completion date
- 1 Oct 2035
- Lead sponsor
- SWOG Cancer Research Network
- NCT number
- NCT07220187
What you commit to
- Study type: Interventional · Phase 3
- Planned participants: 102
- From 4 Aug 2026 to the primary completion date, 1 Oct 2035
- 62 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Who the study is looking for
- 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
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (62)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Our Lady of the Lake Physician Group Coordinator of this site? Confirm its status | Baton Rouge | United States | Recruiting |
| FHCC Overlake Coordinator of this site? Confirm its status | Bellevue | United States | Recruiting |
| Illinois CancerCare-Bloomington Coordinator of this site? Confirm its status | Bloomington | United States | Recruiting |
| Trinity Health IHA Medical Group Hematology Oncology - Brighton Coordinator of this site? Confirm its status | Brighton | United States | Recruiting |
| Illinois CancerCare-Canton Coordinator of this site? Confirm its status | Canton | United States | Recruiting |
| Trinity Health IHA Medical Group Hematology Oncology - Canton Coordinator of this site? Confirm its status | Canton | United States | Recruiting |
| Illinois CancerCare-Carthage Coordinator of this site? Confirm its status | Carthage | United States | Recruiting |
| UNC Lineberger Comprehensive Cancer Center Coordinator of this site? Confirm its status | Chapel Hill | United States | Recruiting |
| Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Coordinator of this site? Confirm its status | Chelsea | United States | Recruiting |
| Siteman Cancer Center at Saint Peters Hospital Coordinator of this site? Confirm its status | City of Saint Peters | United States | Recruiting |
| Siteman Cancer Center at West County Hospital Coordinator of this site? Confirm its status | Creve Coeur | United States | Recruiting |
| Carle at The Riverfront Coordinator of this site? Confirm its status | Danville | United States | Recruiting |
| Decatur Memorial Hospital Coordinator of this site? Confirm its status | Decatur | United States | Recruiting |
| Cancer Care Specialists of Illinois - Decatur Coordinator of this site? Confirm its status | Decatur | United States | Recruiting |
| Duke University Medical Center Coordinator of this site? Confirm its status | Durham | United States | Recruiting |
| Carle Physician Group-Effingham Coordinator of this site? Confirm its status | Effingham | United States | Recruiting |
| Illinois CancerCare-Eureka Coordinator of this site? Confirm its status | Eureka | United States | Recruiting |
| Illinois CancerCare-Galesburg Coordinator of this site? Confirm its status | Galesburg | United States | Recruiting |
| UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care Coordinator of this site? Confirm its status | Irvine | United States | Recruiting |
| Illinois CancerCare-Kewanee Clinic Coordinator of this site? Confirm its status | Kewanee | United States | Recruiting |
| FHCC at EvergreenHealth Coordinator of this site? Confirm its status | Kirkland | United States | Recruiting |
| UCI Health - Laguna Hills Coordinator of this site? Confirm its status | Laguna Hills | United States | Recruiting |
| Trinity Health Saint Mary Mercy Livonia Hospital Coordinator of this site? Confirm its status | Livonia | United States | Recruiting |
| Illinois CancerCare-Macomb Coordinator of this site? Confirm its status | Macomb | United States | Recruiting |
| Carle Physician Group-Mattoon/Charleston Coordinator of this site? Confirm its status | Mattoon | United States | Recruiting |
| Froedtert Menomonee Falls Hospital Coordinator of this site? Confirm its status | Menomonee Falls | United States | Recruiting |
| Medical College of Wisconsin Coordinator of this site? Confirm its status | Milwaukee | United States | Recruiting |
| ProHealth D N Greenwald Center Coordinator of this site? Confirm its status | Mukwonago | United States | Recruiting |
| Froedtert and MCW Moorland Reserve Health Center Coordinator of this site? Confirm its status | New Berlin | United States | Recruiting |
| Carle BroMenn Medical Center Coordinator of this site? Confirm its status | Normal | United States | Recruiting |
| Carle Cancer Institute Normal Coordinator of this site? Confirm its status | Normal | United States | Recruiting |
| Drexel Town Square Health Center Coordinator of this site? Confirm its status | Oak Creek | United States | Recruiting |
| ProHealth Oconomowoc Memorial Hospital Coordinator of this site? Confirm its status | Oconomowoc | United States | Recruiting |
| HSHS Saint Elizabeth's Hospital Coordinator of this site? Confirm its status | O'Fallon | United States | Recruiting |
| Cancer Care Center of O'Fallon Coordinator of this site? Confirm its status | O'Fallon | United States | Recruiting |
| UC Irvine Health- Chao Family Comprehensive Cancer Center Coordinator of this site? Confirm its status | Orange | United States | Recruiting |
| Illinois CancerCare-Ottawa Clinic Coordinator of this site? Confirm its status | Ottawa | United States | Recruiting |
| Illinois CancerCare-Pekin Coordinator of this site? Confirm its status | Pekin | United States | Recruiting |
| Illinois CancerCare-Peoria Coordinator of this site? Confirm its status | Peoria | United States | Recruiting |
| Illinois CancerCare-Peru Coordinator of this site? Confirm its status | Peru | United States | Recruiting |
| Thomas Jefferson University Hospital Coordinator of this site? Confirm its status | Philadelphia | United States | Recruiting |
| Trinity Health Saint Joseph Mercy Oakland Hospital Coordinator of this site? Confirm its status | Pontiac | United States | Recruiting |
| Illinois CancerCare-Princeton Coordinator of this site? Confirm its status | Princeton | United States | Recruiting |
| VCU Massey Cancer Center at Stony Point Coordinator of this site? Confirm its status | Richmond | United States | Recruiting |
| VCU Massey Comprehensive Cancer Center Coordinator of this site? Confirm its status | Richmond | United States | Recruiting |
| Huntsman Cancer Institute/University of Utah Coordinator of this site? Confirm its status | Salt Lake City | United States | Recruiting |
| Fred Hutchinson Cancer Center Coordinator of this site? Confirm its status | Seattle | United States | Recruiting |
| University of Washington Medical Center - Montlake Coordinator of this site? Confirm its status | Seattle | United States | Recruiting |
| FHCC at Northwest Hospital Coordinator of this site? Confirm its status | Seattle | United States | Recruiting |
| Memorial Hospital East Coordinator of this site? Confirm its status | Shiloh | United States | Recruiting |
| Springfield Memorial Hospital Coordinator of this site? Confirm its status | Springfield | United States | Recruiting |
| Southern Illinois University School of Medicine Coordinator of this site? Confirm its status | Springfield | United States | Recruiting |
| Springfield Clinic Coordinator of this site? Confirm its status | Springfield | United States | Recruiting |
| Washington University School of Medicine Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Siteman Cancer Center at Christian Hospital Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Siteman Cancer Center-South County Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Carle Cancer Center Coordinator of this site? Confirm its status | Urbana | United States | Recruiting |
| Illinois CancerCare - Washington Coordinator of this site? Confirm its status | Washington | United States | Recruiting |
| ProHealth Waukesha Memorial Hospital Coordinator of this site? Confirm its status | Waukesha | United States | Recruiting |
| UW Cancer Center at ProHealth Care Coordinator of this site? Confirm its status | Waukesha | United States | Recruiting |
| Froedtert West Bend Hospital/Kraemer Cancer Center Coordinator of this site? Confirm its status | West Bend | United States | Recruiting |
| Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Coordinator of this site? Confirm its status | Ypsilanti | United States | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.