A Phase II Study of Time-limited Combination of Pirtobrutinib, Venetoclax, and Rituximab in Treatment Naïve Patients With Waldenström's Macroglobulinemia (WM) / Lymphoplasmacytic Lymphoma (LPL) (PRoVen)
The purpose of this study is to find out if the combination of pirtobrutinib, venetoclax, and rituximab is an effective treatment for participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL)
• Age greater than or equal to 18 years
• Histologically confirmed treatment naive WM/LPL
• Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm and/ or IgM levels \> 0.5gm/dl quantified by using densitometry on serum protein electrophoresis (SPEP) or quantitative nephelometry.
• Participants must have at least one of the established criteria to require therapy for WM, including anemia, thrombocytopenia, neuropathy related to WM, symptomatic hyperviscosity or serum viscosity levels greater than 4.0 centipoises, WM-associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms
• ECOG performance status ≤2
• Platelet count ≥ 50,000 cells/mm3, independent of transfusions within 7 days of screening assessment
• Hemoglobin ≥ 8 g/dL, unless due to disease involvement in which case ≥ 7 g/dL, independent of transfusions within 7 days of screening assessment
• Absolute neutrophil count \>1000 cells/mcL, independent of growth factor support within 7 days of screening assessment
• Total bilirubin \< 1.5 x upper normal institutional limits. In patients with Gilbert's disease total bilirubin up to 3x ULN will be allowed
• AST(SGOT)/ALT(SGPT) \< 3 x institutional upper limit of normal unless elevation is caused by liver involvement with WM in which case AST and ALT may be ≤ 5 x ULN
• Creatinine within normal institutional limits OR Creatinine clearance \>40 mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements)
• Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN
• Ability to understand and the willingness to sign a written informed consent document.
• Patient must be able to swallow pills
• Patients with Hepatitis B surface antibody serum positivity due to prior immunization, as well as those with Hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible.
• Willingness of participants of reproductive potential and their partners to observe highly effective birth control methods for the duration of treatment and for 1 year following the last dose of study treatment