NCT07231952

Brief Summary

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)

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
23mo left

Started Nov 2025

Geographic Reach
1 country

8 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress20%
Nov 2025Apr 2028

Study Start

First participant enrolled

November 11, 2025

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

November 13, 2025

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 17, 2025

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 11, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 11, 2028

Last Updated

November 17, 2025

Status Verified

November 1, 2025

Enrollment Period

2.4 years

First QC Date

November 13, 2025

Last Update Submit

November 13, 2025

Conditions

Waldenstrom MacroglobulinemiaLymphoplasmacytic Lymphoma

Keywords

Waldenstrom MacroglobulinemiaLymphoplasmacytic LymphomaMemorial Sloan Kettering Cancer Center25-149

Outcome Measures

Primary Outcomes (1)

  • Number of participants with Very Good Partial Response Rate or Better

    To evaluate the rate of very good partial response (VGPR) rate or better in previously untreated participants with WM / LPL who are treated upfront with this regimen.

    1 year

Study Arms (1)

Participants with Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)

EXPERIMENTAL

Participants with treatment naive Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)

Drug: PirtobrutinibDrug: VenetoclaxDrug: Rituximab

Interventions

PirtobrutinibDRUG

PO QD

Participants with Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
VenetoclaxDRUG

PO QD

Participants with Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
RituximabDRUG

IV or SC

Participants with Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

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.
  • +1 more criteria

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
  • +24 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Beth Israel Deaconess Medical Center (Data Collection Only)

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memoral Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Waldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal Zone

Interventions

pirtobrutinibvenetoclaxRituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • M. Lia Palomba, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

M. Lia Palomba, MD

CONTACT

646-608-3711Palombam@MSKCC.ORG

Jennifer Lue, MD

CONTACT

646-608-4160luej@mskcc.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 13, 2025

First Posted

November 17, 2025

Study Start

November 11, 2025

Primary Completion (Estimated)

April 11, 2028

Study Completion (Estimated)

April 11, 2028

Last Updated

November 17, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Locations

US(8)