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

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

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood and buccal swab sample collection

PROCEDURE

Computed Tomography

Undergo CT scan and/or PET/CT scan

DRUG

Cyclophosphamide

Given IV

DRUG

Doxorubicin Hydrochloride

Given IV

PROCEDURE

Echocardiography Test

Undergo echocardiography

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA scan

DRUG

Pirtobrutinib

Given PO

PROCEDURE

Positron Emission Tomography

Undergo PET/CT scan

DRUG

Prednisone

Given PO

BIOLOGICAL

Rituximab

Given IV

BIOLOGICAL

Rituximab and Hyaluronidase Human

Given SC

OTHER

Survey Administration

Ancillary studies

DRUG

Vincristine

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• SWOG Cancer Research Network

  lead NETWORK

Principal Investigators

• Mazyar Shadman · SWOG Cancer Research Network

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-02

Primary Completion

2035-10-01

Completion

2036-10-31

FDA Drug

Yes