What side effects are associated with this type of intervention?

Common side effects of BTK inhibitors (such as ibrutinib and acalabrutinib) include neutropenia, diarrhea, hypertension, and atrial fibrillation. BCL-2 inhibitors like venetoclax are associated with neutropenia, infections, and tumor lysis syndrome. Both classes of drugs can cause gastrointestinal disturbances and fatigue. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

For the treatment of Mantle Cell Lymphoma (MCL), the FDA has approved several drugs, including BTK inhibitors like Ibrutinib and Acalabrutinib. Ibrutinib was one of the first BTK inhibitors approved for MCL and has shown significant efficacy in relapsed or refractory cases. Acalabrutinib, another BTK inhibitor, offers a similar mechanism of action with potentially different side effect profiles. Venetoclax, a BCL-2 inhibitor, has also been explored in combination therapies for MCL, although its primary approval is for chronic lymphocytic leukemia (CLL). These drugs represent a targeted approach to treating MCL by inhibiting key pathways involved in cancer cell survival and proliferation.

What other types of research exist?

Promising novel alternatives for Mantle Cell Lymphoma patients in 2024 include: <ol> <li>Bendamustine plus Rituximab: This combination has shown high efficacy and a favorable toxicity profile in relapsed/refractory MCL.</li> <li>Bortezomib-based Regimens: Bortezomib combined with Rituximab and Dexamethasone has demonstrated significant activity in relapsed and refractory MCL.</li> <li>CAR-T Cell Therapy: Chimeric Antigen Receptor T cell therapy is an emerging option for relapsed/refractory MCL, particularly for patients who have not responded to other treatments.</li> <li>Ibrutinib: Another BTK inhibitor that has been effective in MCL, often used in combination with Rituximab.</li> <li>Lenalidomide: An immunomodulatory drug that has shown promise in combination with Rituximab for relapsed/refractory MCL.</li> </ol>

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Pirtobrutinib + Venetoclax for Mantle Cell Lymphoma

Phase 2

Recruiting

Led By Preetesh Jain, MD, DM, PhD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, pirtobrutinib and venetoclax, to treat patients with mantle cell lymphoma that has come back or not responded to other treatments. Pirtobrutinib stops cancer cells from growing, while venetoclax makes them die. Venetoclax has been previously studied in children with recurring or resistant cancers and in combination with other drugs for mantle cell lymphoma.

Who is the study for?

Adults with relapsed or refractory Mantle Cell Lymphoma (MCL) who have measurable disease, an ECOG performance status of 2 or less, and adequate organ function. They must not be pregnant or breastfeeding, agree to use effective contraception, and cannot have central nervous system involvement by lymphoma, uncontrolled infections like HIV/HBV/HCV, significant heart issues, bleeding disorders, or other severe medical conditions.

What is being tested?

The trial is testing the effectiveness of combining two drugs—Pirtobrutinib and Venetoclax—in treating MCL that has either returned after treatment or hasn't responded to previous therapies. The goal is to see if this drug combination can better control the disease.

What are the potential side effects?

Potential side effects may include digestive disturbances such as nausea and diarrhea; blood-related issues like anemia; increased risk of infection due to immune suppression; liver enzyme alterations suggesting liver impact; fatigue; possible allergic reactions to medication components.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2022 Phase 1 trial • 32 Patients • NCT05176314

Headache

100%

80%

60%

40%

20%

Study treatment Arm

20 mg Rosuvastatin (Day 1)

20 mg Rosuvastatin + 200 mg Pirtobrutinib (Day 13)

20 mg Rosuvastatin + 200 mg Pirtobrutinib (Day 6)

200 mg Pirtobrutinib QD (Days 7-12)

200 mg Pirtobrutinib QD (Days 14-17)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Pirtobrutinib (LOXO-305) and Venetoclax (combination)Experimental Treatment2 Interventions

Participants will have study visits every week during Cycle 1, and then on Day 1 of every cycle for the first year. After that, they will have study visits on Day 1 of every 2 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pirtobrutinib

2020

Completed Phase 1

~240

Venetoclax

2019

Completed Phase 3

~2240

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Mantle Cell Lymphoma (MCL) treatments often include BTK inhibitors and BCL-2 inhibitors. BTK inhibitors, such as Pirtobrutinib, block Bruton's tyrosine kinase, a protein essential for B-cell receptor signaling, thereby inhibiting the growth and survival of malignant B-cells. BCL-2 inhibitors, like Venetoclax, target the BCL-2 protein, which prevents apoptosis (cell death) in cancer cells. By inhibiting BCL-2, Venetoclax promotes the death of these malignant cells. These mechanisms are crucial for MCL patients as they directly target the pathways that allow cancer cells to proliferate and survive, offering a more effective and targeted approach to treatment.

Venetoclax: evidence to date and clinical potential.