40 Participants Needed

Pirtobrutinib + Venetoclax + Rituximab for Waldenström's Macroglobulinemia

Recruiting at 7 trial locations
ML
JL
Overseen ByJennifer Lue, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new combination of treatments—pirtobrutinib, venetoclax, and rituximab—can effectively treat Waldenström's macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL), rare types of blood cancer. The goal is to determine if this combination can manage symptoms and slow disease progression. Individuals who have not received previous treatment for WM or LPL and experience symptoms like anemia or nerve problems related to the disease might be suitable candidates. Joining the trial offers the opportunity to try a promising new therapy before it becomes widely available. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who require ongoing use of certain drugs that affect liver enzymes (CYP3A inducers or inhibitors) or P-gp inhibitors. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety of combining three drugs—pirtobrutinib, venetoclax, and rituximab—for individuals with Waldenström's macroglobulinemia (WM). Earlier studies have shown that venetoclax alone was safe and effective for patients whose WM had returned, yielding good results without serious side effects.

Additionally, when pirtobrutinib and venetoclax were used together in previously treated patients, they were well-tolerated. This suggests that using these drugs together might be manageable for patients.

Although this specific combination remains under study, the safe use of venetoclax and pirtobrutinib in other contexts is reassuring. However, it is important to note that this research is ongoing, and participants will be closely monitored for any side effects during the trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pirtobrutinib, Venetoclax, and Rituximab for treating Waldenström's Macroglobulinemia because it offers a novel approach compared to standard therapies like chemotherapy or single-agent immunotherapy. Pirtobrutinib is a next-generation BTK inhibitor that targets cancer cells more precisely, potentially leading to fewer side effects and improved effectiveness. Venetoclax works by inducing cancer cell death through a different pathway, offering a complementary mechanism to Pirtobrutinib. Rituximab, a well-known antibody, enhances the treatment by targeting and killing cancerous B-cells. This combination could provide a more comprehensive attack on the disease, offering hope for better outcomes.

What evidence suggests that this trial's treatments could be effective for Waldenström's macroglobulinemia?

This trial will evaluate the combination of pirtobrutinib, venetoclax, and rituximab for treating Waldenström's macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). Studies have shown that this combination looks promising. In earlier small studies, patients treated with venetoclax showed positive results, especially those with recurrent or hard-to-treat cancer. Research also shows that using pirtobrutinib and venetoclax together was effective in patients who had already received treatment for WM, with many experiencing significant improvement. Additionally, BTK inhibitors like pirtobrutinib have been found to work well in both newly diagnosed and previously treated patients. These findings suggest that this combination of drugs could be effective for WM and LPL.12356

Who Is on the Research Team?

ML

M. Lia Palomba, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Waldenström's macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL), including MALT Lymphoma. Specific eligibility criteria are not provided, but typically include factors like age, disease stage, and overall health.

Inclusion Criteria

My Waldenstrom's macroglobulinemia/LPL has not been treated yet.
Platelet count ≥ 50,000 cells/mm3, independent of transfusions 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
See 13 more

Exclusion Criteria

Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to any intended study medications
Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33)
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
See 18 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of pirtobrutinib, venetoclax, and rituximab

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Pirtobrutinib
  • Rituximab
  • Venetoclax
Trial Overview The study is testing the effectiveness of a combination treatment using Pirtobrutinib, Venetoclax, and Rituximab in patients with WM/LPL to see if it can effectively manage their condition.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Participants with Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)Experimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Eli Lilly and Company

Industry Sponsor

Trials
2,708
Recruited
3,720,000+
Dr. Daniel Skovronsky profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

AbbVie

Industry Sponsor

Trials
1,079
Recruited
535,000+
Founded
2013
Headquarters
North Chicago, USA
Known For
Immunology treatments
Top Products
Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael profile image

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Citations

A Study of Pirtobrutinib, Venetoclax, and Rituximab in ...... venetoclax, and rituximab is an effective treatment for participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL).
A Phase 2 Study of Pirtobrutinib, Venetoclax, and ...Researchers want to see how well pirtobrutinib, venetoclax, and rituximab work together in people with Waldenström's macroglobulinemia (WM) who have not been ...
Outcomes of patients with relapsed/refractory ...Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM).
A Phase II Study of Pirtobrutinib and Venetoclax in ...The combination of pirtobrutinib and venetoclax appears active in symptomatic, previously treated WM patients with a VGPR rate of 56%, exceeding the futility ...
Optimal use of BTK inhibitors in Waldenström's ...It is notable that the efficacy of BTKi, including ibrutinib and newer BKTis, seems to be similar in previously untreated and previously treated patients with ...
Long-term follow-up of venetoclax monotherapy in previously ...The B-cell lymphoma 2 (BCL2) antagonist venetoclax is safe and effective for patients with relapsed Waldenström Macroglobulinemia (WM) and is ...
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