PRV Combination Therapy for Mantle Cell Lymphoma

Overseen By Michael Wang, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, CYP3A inducers, P-gp inhibitors, Anticoagulants

Disqualifiers: CNS involvement, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires a 3-day washout period (time without taking certain medications) for corticosteroids if they were used for acute MCL-related symptoms. Additionally, you cannot use certain medications like strong CYP3A inhibitors or inducers, grapefruit products, or vitamin K antagonists shortly before or during the study. Please consult with the trial team to discuss your specific medications.

What data supports the effectiveness of the drug combination therapy for Mantle Cell Lymphoma?

Research shows that combining venetoclax with other drugs like ibrutinib has been effective in treating relapsed or refractory mantle cell lymphoma, with a high overall response rate and manageable side effects. Additionally, venetoclax combined with rituximab has shown promising results in treating chronic lymphocytic leukemia, suggesting potential benefits for similar conditions. ^{1 2 3 4 5}

What makes the PRV combination therapy for mantle cell lymphoma unique?

The PRV combination therapy for mantle cell lymphoma is unique because it combines Pirtobrutinib, Rituximab, and Venetoclax, which target different pathways in cancer cells, potentially offering a more effective treatment by attacking the cancer from multiple angles. This combination is novel as it includes Pirtobrutinib, a newer Bruton's tyrosine kinase inhibitor, which may provide benefits over existing treatments that use older BTK inhibitors like Ibrutinib. ^{1 2 3 4 5}

What is the purpose of this trial?

Primary Objectives: To estimate the percent of participants who achieve a best response of complete response by the end of the PRV combination therapy in the induction therapy phase in patients with previously untreated MCL.

Research Team

Michael Wang, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with previously untreated Mantle Cell Lymphoma (MCL). Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments that could interfere with the study.

Inclusion Criteria

I need treatment for my condition.

My cancer is confirmed as MCL with specific genetic features.

I have not had any treatment or radiotherapy for my MCL.

Exclusion Criteria

I do not have any severe illnesses besides my current condition.

Pregnant or planning pregnancy

I do not have any current or recent infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive Pirtobrutinib, Rituximab, and Venetoclax combination therapy to achieve a complete response

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Pirtobrutinib
• Rituximab
• Venetoclax

Trial Overview The GATE1 trial is testing a combination of three drugs: Pirtobrutinib, Rituximab, and Venetoclax in people with MCL. The main goal is to see how many patients achieve complete disappearance of cancer signs after this treatment regimen during the initial therapy phase.

Participant Groups

Group I: Pirtobrutinib, Rituximab and Venetoclax combination Experimental Treatment 3 Interventions

Pirtobrutinib is already approved in United States for the following indications:

Approved in United States as Jaypirca for:

• Mantle Cell Lymphoma
• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

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

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a retrospective analysis of 4 patients with relapsed/refractory mantle-cell lymphoma (MCL), the combination of ibrutinib and venetoclax resulted in a 50% complete response rate, demonstrating its potential efficacy as a treatment option.

All patients who responded to the treatment were able to undergo allogeneic stem cell transplantation, with two patients remaining in complete remission, indicating that this combination therapy may be a viable bridge to transplant for MCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in association with venetoclax for the treatment of mantle-cell lymphoma: a multicenter case series. Fabbri, A., Cencini, E., Congiu, AG., et al.[2021]

The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.

Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. Wanner, D., Steurer, M.[2020]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Ibrutinib has shown durable efficacy in treating relapsed/refractory chronic lymphocytic leukemia (CLL) over a 7-year follow-up, but patients with certain health conditions like cardiac disease or those on anticoagulants may not be suitable for this continuous therapy.

Venetoclax combined with rituximab offers an effective, chemo-free treatment option for R/R CLL with a fixed duration of up to 24 months, achieving deep responses in most patients and demonstrating a reassuring safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Chronic Lymphocytic Leukemia: Chemoimmunotherapy, Treatment until Progression with Mechanism-Driven Agents or Finite-Duration Therapy? Cuneo, A., Foà, R.[2020]

The combination of venetoclax (VEN) and ibrutinib (IBR) showed a high overall response rate of 93.8% at the optimal dosing of VEN 200 mg and IBR 420 mg in treating relapsed mantle cell lymphoma (MCL) among 35 participants.

The study found that higher doses of VEN and IBR did not improve efficacy and were associated with increased toxicity, highlighting the importance of dose optimization in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. Portell, CA., Wages, NA., Kahl, BS., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib in association with venetoclax for the treatment of mantle-cell lymphoma: a multicenter case series. [2021]

2. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Chronic Lymphocytic Leukemia: Chemoimmunotherapy, Treatment until Progression with Mechanism-Driven Agents or Finite-Duration Therapy? [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. [2022]