Recruiting
Phase 3

Pirtobrutinib & R-CHOP

Sponsor:

SWOG Cancer Research Network

Code:

NCT07220187

Conditions

Richter Syndrome

Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma

Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Cyclophosphamide

Doxorubicin Hydrochloride

Echocardiography Test

Study Details

Brief 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.

Conditions

Richter Syndrome

Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma

Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma

Study ID

NCT07220187

Start date

Aug 4, 2026

Status verified date

Oct, 2026

Completion date

Oct, 2036

Anticipated

Primary completion date

Oct 1, 2035

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

102 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (pirtobrutinib and R-CHOP)

Patients receive pirtobrutinib PO QD on days 1-21 of each cycle, rituximab IV or rituximab hyaluronidase SC (starting with cycle 2), cyclophosphamide IV on day 1 of each cycle, doxorubicin IV on day 1 of each cycle, vincristine IV on day 1 of each cycle, and prednisone PO QD on days 1-5 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients continue to receive pirtobrutinib PO QD on days 1-21 of each cycle for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or symptomatic deterioration may receive 1 additional cycle as long as the participant is continuing to clinically benefit from treatment in the opinion of the treating investigator. Patients undergo echocardiography or MUGA scan and buccal swab collection during screening, as well as CT scan and/or PET/CT, and blood sample collection throughout the study.

active comparator: Arm II (R-CHOP)

Patients receive rituximab IV or rituximab hyaluronidase SC (starting with cycle 2), cyclophosphamide IV on day 1 of each cycle, doxorubicin IV on day 1 of each cycle, vincristine IV on day 1 of each cycle, and prednisone PO QD on days 1-5 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan and buccal swab collection during screening, as well as CT scan and/or PET, and blood sample collection throughout the study.

Interventions

Biospecimen Collection

Undergo blood and buccal swab sample collection

Computed Tomography

Undergo CT scan and/or PET/CT scan

Cyclophosphamide

Given IV

Doxorubicin Hydrochloride

Given IV

Echocardiography Test

Undergo echocardiography

Multigated Acquisition Scan

Undergo MUGA scan

Pirtobrutinib

Given PO

Positron Emission Tomography

Undergo PET/CT scan

Prednisone

Given PO

Rituximab

Given IV

Rituximab and Hyaluronidase Human

Given SC

Survey Administration

Ancillary studies

Vincristine

Given IV

Primary outcome measure

  • Progression free survival (PFS) [ Time Frame: Up to 7 years ]
  • Overall free survival [ Time Frame: Up to 7 years ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Catherine C. Coombs

UCI Health Laguna Hills

Recruiting

Laguna Hills, California, United States, 92653

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Catherine C. Coombs

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Catherine C. Coombs

Illinois CancerCare-Bloomington

Recruiting

Bloomington, Illinois, United States, 61704

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Canton

Recruiting

Canton, Illinois, United States, 61520

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Carthage

Recruiting

Carthage, Illinois, United States, 62321

Contacts

Principal Investigator:

Bryan A. Faller

Carle at The Riverfront

Recruiting

Danville, Illinois, United States, 61832

Contacts

Principal Investigator:

Suparna Mantha

Cancer Care Specialists of Illinois - Decatur

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Principal Investigator:

Bryan A. Faller

Decatur Memorial Hospital

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Principal Investigator:

Bryan A. Faller

Carle Physician Group-Effingham

Recruiting

Effingham, Illinois, United States, 62401

Contacts

Principal Investigator:

Suparna Mantha

Illinois CancerCare-Eureka

Recruiting

Eureka, Illinois, United States, 61530

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Galesburg

Recruiting

Galesburg, Illinois, United States, 61401

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Kewanee Clinic

Recruiting

Kewanee, Illinois, United States, 61443

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Macomb

Recruiting

Macomb, Illinois, United States, 61455

Contacts

Principal Investigator:

Bryan A. Faller

Carle Physician Group-Mattoon/Charleston

Recruiting

Mattoon, Illinois, United States, 61938

Contacts

Principal Investigator:

Suparna Mantha

Carle BroMenn Medical Center

Recruiting

Normal, Illinois, United States, 61761

Contacts

Principal Investigator:

Suparna Mantha

Carle Cancer Institute Normal

Recruiting

Normal, Illinois, United States, 61761

Contacts

Principal Investigator:

Suparna Mantha

Cancer Care Center of O'Fallon

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Principal Investigator:

Bryan A. Faller

HSHS Saint Elizabeth's Hospital

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Ottawa Clinic

Recruiting

Ottawa, Illinois, United States, 61350

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Pekin

Recruiting

Pekin, Illinois, United States, 61554

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peoria

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peru

Recruiting

Peru, Illinois, United States, 61354

Contacts

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Princeton

Recruiting

Princeton, Illinois, United States, 61356

Contacts

Principal Investigator:

Bryan A. Faller

Memorial Hospital East

Recruiting

Shiloh, Illinois, United States, 62269

Contacts

Principal Investigator:

Dilan A. Patel

Southern Illinois University School of Medicine

Recruiting

Springfield, Illinois, United States, 62702

Contacts

Site Public Contact

217-545-7929

Principal Investigator:

Bryan A. Faller

Springfield Clinic

Recruiting

Springfield, Illinois, United States, 62702

Contacts

Site Public Contact

800-444-7541

Principal Investigator:

Bryan A. Faller

Springfield Memorial Hospital

Recruiting

Springfield, Illinois, United States, 62781

Contacts

Principal Investigator:

Bryan A. Faller

Carle Cancer Center

Recruiting

Urbana, Illinois, United States, 61801

Contacts

Principal Investigator:

Suparna Mantha

Illinois CancerCare - Washington

Recruiting

Washington, Illinois, United States, 61571

Contacts

Principal Investigator:

Bryan A. Faller

Our Lady of the Lake Physician Group

Recruiting

Baton Rouge, Louisiana, United States, 70808

Contacts

Principal Investigator:

Nakhle S. Saba

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Recruiting

Brighton, Michigan, United States, 48114

Contacts

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology - Canton

Recruiting

Canton, Michigan, United States, 48188

Contacts

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Recruiting

Chelsea, Michigan, United States, 48118

Contacts

Principal Investigator:

Tareq Al baghdadi

Trinity Health Saint Mary Mercy Livonia Hospital

Recruiting

Livonia, Michigan, United States, 48154

Contacts

Principal Investigator:

Tareq Al baghdadi

Trinity Health Saint Joseph Mercy Oakland Hospital

Recruiting

Pontiac, Michigan, United States, 48341

Contacts

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Recruiting

Ypsilanti, Michigan, United States, 48197

Contacts

Principal Investigator:

Tareq Al baghdadi

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Principal Investigator:

Dilan A. Patel

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Principal Investigator:

Dilan A. Patel

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Principal Investigator:

Dilan A. Patel

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Principal Investigator:

Dilan A. Patel

Siteman Cancer Center at Christian Hospital

Recruiting

St Louis, Missouri, United States, 63136

Contacts

Principal Investigator:

Dilan A. Patel

UNC Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Principal Investigator:

Christopher E. Jensen

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Public Contact

888-275-3853

Principal Investigator:

Andrea Sitlinger

Thomas Jefferson University Hospital

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contacts

Principal Investigator:

Michael Wysota

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Principal Investigator:

Boyu Hu

VCU Massey Cancer Center at Stony Point

Recruiting

Richmond, Virginia, United States, 23235

Contacts

Site Public Contact

ctoclinops@vcu.edu

Principal Investigator:

Victor Y. Yazbeck

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Principal Investigator:

Victor Y. Yazbeck

FHCC Overlake

Recruiting

Bellevue, Washington, United States, 98004

Contacts

Site Public Contact

425-454-2148

Principal Investigator:

Jason Comer

FHCC at EvergreenHealth

Recruiting

Kirkland, Washington, United States, 98034

Contacts

Site Public Contact

425-899-6000

Principal Investigator:

Vikram Raghunathan

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Site Public Contact

800-804-8824

Principal Investigator:

Mazyar Shadman

FHCC at Northwest Hospital

Recruiting

Seattle, Washington, United States, 98133

Contacts

Site Public Contact

206-606-5800

Principal Investigator:

Paul S. Martin

University of Washington Medical Center - Montlake

Recruiting

Seattle, Washington, United States, 98195

Contacts

Site Public Contact

800-804-8824

Principal Investigator:

Mazyar Shadman

Froedtert Menomonee Falls Hospital

Recruiting

Menomonee Falls, Wisconsin, United States, 53051

Contacts

Site Public Contact

262-257-5100

Principal Investigator:

Gulrayz Ahmed

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-805-3666

Principal Investigator:

Gulrayz Ahmed

ProHealth D N Greenwald Center

Recruiting

Mukwonago, Wisconsin, United States, 53149

Contacts

Site Public Contact

research.institute@phci.org

Principal Investigator:

Timothy R. Wassenaar

Froedtert and MCW Moorland Reserve Health Center

Recruiting

New Berlin, Wisconsin, United States, 53151

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Gulrayz Ahmed

Drexel Town Square Health Center

Recruiting

Oak Creek, Wisconsin, United States, 53154

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Gulrayz Ahmed

ProHealth Oconomowoc Memorial Hospital

Recruiting

Oconomowoc, Wisconsin, United States, 53066

Contacts

Site Public Contact

262-928-7878

Principal Investigator:

Timothy R. Wassenaar

ProHealth Waukesha Memorial Hospital

Recruiting

Waukesha, Wisconsin, United States, 53188

Contacts

Site Public Contact

262-928-7632

Principal Investigator:

Timothy R. Wassenaar

UW Cancer Center at ProHealth Care

Recruiting

Waukesha, Wisconsin, United States, 53188

Contacts

Principal Investigator:

Timothy R. Wassenaar

Froedtert West Bend Hospital/Kraemer Cancer Center

Recruiting

West Bend, Wisconsin, United States, 53095

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Gulrayz Ahmed

More Information

Sponsor

SWOG Cancer Research Network

Last update posted

Oct 13, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-14. This information was provided to ClinicalTrials.gov by SWOG Cancer Research Network on 2026-10-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.