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

Sponsor
SWOG Cancer Research Network
Study ID
NCT07220187
Phase
PHASE3
Status
Not Yet Recruiting

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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 Years - N/A
Healthy Volunteers
Not accepted

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

Study Details

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 Dates

Start date
Aug 31, 2026
Status verified
Jun 2026
Primary completion
Oct 1, 2035
Completion
Oct 31, 2036

Study Design

Enrollment
102 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

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.

Primary Outcome Measure

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

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