Study on Pirtobrutinib, Venetoclax, and Rituximab for Treating Waldenström's Macroglobulinemia (WM) and Lymphoplasmacytic Lymphoma (LPL)

Inclusion Criteria

• Must be 18 years or older.
• Have a confirmed diagnosis of untreated Waldenström's Macroglobulinemia (WM) or Lymphoplasmacytic Lymphoma (LPL).
• Have measurable disease, such as a lymph node 1.5 cm or larger, or specific IgM levels.
• Must need treatment for WM due to symptoms like anemia, low platelet count, nerve problems, or other related conditions.
• Be in good overall health with an ECOG performance status of 0 to 2.
• Have adequate blood counts and organ function as determined by specific tests.
• Be able to swallow pills.
• Have controlled Hepatitis B if previously exposed, with negative PCR results.
• Agree to use effective birth control during the study and for one year after the last dose.

Exclusion Criteria

• Have had any prior systemic therapy for WM/LPL.
• Have had major surgery within four weeks before starting treatment.
• Have a history of significant bleeding disorders or recent major bleeding events.
• Have had a stroke or brain bleeding within six months before starting treatment.
• Have had a stem cell transplant or CAR-T therapy recently or have related complications.
• Have significant heart disease or uncontrolled heart rhythm problems.
• Have a prolonged QT interval on an ECG.
• Have active HIV, Hepatitis B, or Hepatitis C infections.
• Be pregnant or breastfeeding, or planning to become pregnant or breastfeed during the study.
• Have conditions affecting drug absorption or other uncontrolled medical issues.
• Have another active cancer unless in remission with a life expectancy over two years.
• Require blood thinners like warfarin.
• Have received a live vaccine within 28 days before starting treatment.
• Have allergies to study drugs or require certain medications that interact with the study drugs.