Actively Recruiting
A Phase II Study of Time-limited Combination of Pirtobrutinib, Venetoclax, and Rituximab in Treatment Na ve Patients With Waldenstr m's Macroglobulinemia / Lymphoplasmacytic Lymphoma (PRoVen)
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-06-03
40
Participants Needed
9
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Memorial Sloan Kettering Cancer Center
Lead Sponsor
A
AbbVie
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of three drugs—pirtobrutinib, venetoclax, and rituximab—as a treatment for people with Waldenstr m's macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL) who have not received previous treatment. This Phase II study aims to determine if this time-limited drug combination can effectively treat these conditions, which involve abnormal immune cell growth. Participants will receive pirtobrutinib and venetoclax as daily oral pills, while rituximab will be given either by intravenous or subcutaneous injection. The study focuses on treatment-na ve patients and monitors their response to this combination over the trial period. During the study, participants will be closely monitored for their response to treatment, specifically looking at the number achieving a very good partial response or better within one year. Assessments will include blood tests, physical exams, and other evaluations to track disease status and safety. The total duration and follow-up details are aligned with the study's timelines and procedures.
CONDITIONS
Brief Title
A Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age greater than or equal to 18 years
- Histologically confirmed treatment naive Waldenstr�m's Macroglobulinemia or Lymphoplasmacytic Lymphoma
- Measurable disease with at least one lymph node 1.5 cm and/or IgM levels > 0.5 gm/dl measured by serum protein electrophoresis or quantitative nephelometry
- At least one established criterion requiring therapy for WM, such as anemia, thrombocytopenia, neuropathy, symptomatic hyperviscosity, serum viscosity > 4.0 centipoises, WM-related kidney disease, bulky disease, or constitutional symptoms
- ECOG performance status 2
- Platelet count 50,000 cells/mm3 within 7 days of screening
- Hemoglobin 8 g/dL or 7 g/dL if due to disease involvement, within 7 days of screening
- Absolute neutrophil count >1000 cells/mcL within 7 days of screening
- Total bilirubin < 1.5 x upper normal limit (up to 3x ULN allowed in Gilbert's disease)
- AST/ALT < 3 x upper normal limit (up to 5x if liver involvement with WM)
- Creatinine normal or creatinine clearance >40 mL/min
- Adequate coagulation with aPTT/PT/INR not greater than 1.5 x ULN
- Ability and willingness to sign informed consent
- Ability to swallow pills
- Hepatitis B surface antibody positive due to immunization or core antibody positive with negative PCR on antiviral therapy allowed
- Willingness to use highly effective birth control during treatment and for 1 year after last dose
You will not qualify if you...
- Prior systemic therapy for WM or LPL
- Major surgery within 4 weeks before starting treatment
- History of bleeding diathesis or major bleeding events
- Grade 3 arrhythmia on prior BTK inhibitor treatment
- Stroke or intracranial hemorrhage within 6 months before treatment
- Stem cell transplant or CAR-T therapy within 60 days before treatment or active complications from these treatments
- Significant heart disease including unstable angina, recent heart attack, low heart function, severe heart failure, or uncontrolled arrhythmias
- QT interval corrected for heart rate > 470 msec (unless corrected safely)
- Positive HIV test
- Active hepatitis B or C infection
- Active cytomegalovirus infection
- Pregnancy or breastfeeding or plans to become pregnant or breastfeed during and shortly after the study
- Active malabsorption or gastrointestinal conditions affecting drug absorption
- Other uncontrolled infections or diseases posing risk
- Active autoimmune cytopenia with recent therapy changes
- Active second cancer unless in remission with life expectancy over 2 years
- Need for therapeutic anticoagulation with warfarin or vitamin K antagonists
- Vaccination with live vaccines within 28 days before treatment
- Known allergy to study drugs or ingredients
- Recent use or need for strong CYP3A or P-gp inhibitors or inducers within 7 days before first dose
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Time-limited treatment period as defined by the study protocol
Participants receive a time-limited combination of Pirtobrutinib, Venetoclax, and Rituximab to treat Waldenström's Macroglobulinemia or Lymphoplasmacytic Lymphoma.
Regular visits during treatment for drug administration and monitoring
Trial Site Locations
Total: 9 locations
1
Dana Farber Cancer Institute (Data Collection and Specimen Analysis)
Boston, Massachusetts, United States, 02115
Actively Recruiting
2
Beth Israel Deaconess Medical Center (Data Collection Only)
Boston, Massachusetts, United States, 02215
Not Yet Recruiting
3
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
4
Memoral Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
Actively Recruiting
5
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States, 07645
Actively Recruiting
6
Memorial Sloan Kettering Suffolk - Commack
Commack, New York, United States, 11725
Actively Recruiting
7
Memorial Sloan Kettering Westchester
Harrison, New York, United States, 10604
Actively Recruiting
8
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
9
Memorial Sloan Kettering Nassau
Uniondale, New York, United States, 11553
Actively Recruiting
Research Team
M
M. Lia Palomba, MD
J
Jennifer Lue, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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