A Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)

Recruiting now · Phase 2

Conditions studied: Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma

In brief

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)

Key facts

Study ID

NCT07231952

Run by

Memorial Sloan Kettering Cancer Center

People needed

40

Starts

2025-11-11

Expected to finish

2028-04-11

Last updated by the study team

2026-06-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• Prior/Concomitant Therapy: Participants must not have had prior systemic therapy.
• Medical Conditions
• Major surgery within 4 weeks prior to start of treatment
• History of bleeding diathesis
• Patients who 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)
• History of stroke or intracranial hemorrhage within 6 months of start of treatment
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within 60 days of start of treatment or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing:
• active graft versus host disease (GVHD);
• cytopenia from incomplete blood cell count recovery post-transplant;
• need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
• ongoing immunosuppressive therapy (> 20 mg prednisone or equivalent daily).
• Significant cardiovascular disease defined as:
• unstable angina or acute coronary syndrome within the past 2 months prior to start of treatment
• history of myocardial infarction within 3 months prior to start of treatment or
• documented LVEF by any method of ≤ 40% in the 12 months prior to start of treatment
• ≥ Grade 3 NYHA functional classification system of heart failure
• Uncontrolled or symptomatic arrhythmias
• Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33).
• Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
• Correction for underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
• Patients who have tested positive for Human Immunodeficiency Virus (HIV) are excluded due to risk of opportunistic infections with both HIV and BTK- inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrollment.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below:
• Hepatitis B virus (HBV):
• Patients with positive hepatitis B surface antigen (HBsAg) are excluded.

Where it is running

• Dana Farber Cancer Institute (Data Collection and Specimen Analysis) — Boston, Massachusetts, United States (enrolling)
• Beth Israel Deaconess Medical Center (Data Collection Only) — Boston, Massachusetts, United States (enrolling)
• Memorial Sloan Kettering Basking Ridge — Basking Ridge, New Jersey, United States (enrolling)
• Memoral Sloan Kettering Monmouth — Middletown, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Bergen — Montvale, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Suffolk - Commack — Commack, New York, United States (enrolling)
• Memorial Sloan Kettering Westchester — Harrison, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Nassau — Uniondale, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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