PRV Combination Therapy for Mantle Cell Lymphoma

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three drugs—Pirtobrutinib, Rituximab, and Venetoclax—to determine their effectiveness in treating mantle cell lymphoma (MCL), a type of blood cancer. The main goal is to assess how many participants achieve a complete response, meaning no signs of the disease, after treatment. The trial seeks individuals who have not yet received treatment for MCL and have specific disease features, such as positive CD20 markers, which a doctor can confirm. Participants should also exhibit symptoms requiring treatment, like B symptoms or enlarged lymph nodes. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the combination of pirtobrutinib, rituximab, and venetoclax is generally well-tolerated by patients with mantle cell lymphoma (MCL). Previous patients have found these drugs effective against MCL, with manageable side effects.

Pirtobrutinib is a newer drug, but studies in similar situations have not revealed major safety concerns. Rituximab and venetoclax are more established and commonly used to treat various blood cancers. Rituximab can sometimes cause mild reactions like fever or chills, while venetoclax can lead to low blood counts, which doctors monitor closely.

Overall, studies have used this combination of treatments without unexpected safety issues. The evidence suggests this treatment plan is fairly safe for people with untreated MCL. However, side effects can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for mantle cell lymphoma because it combines three powerful drugs: Pirtobrutinib, Rituximab, and Venetoclax. Each of these drugs has a distinct way of attacking cancer cells. Pirtobrutinib is a next-generation BTK inhibitor that targets a key enzyme in cancer cell survival, potentially offering effectiveness even in patients who have become resistant to other BTK inhibitors. Rituximab is a monoclonal antibody that helps the immune system find and destroy cancer cells, while Venetoclax targets BCL-2 proteins, encouraging cancer cells to self-destruct. This combination could offer a more comprehensive approach to treatment, possibly improving outcomes for patients who don’t respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for Mantle Cell Lymphoma?

Research shows that the combination of pirtobrutinib, rituximab, and venetoclax, which participants in this trial will receive, may be promising for treating mantle cell lymphoma (MCL). This combination has produced strong responses in patients with similar conditions, such as chronic lymphocytic leukemia (CLL). Pirtobrutinib blocks a protein that aids cancer cell growth. Rituximab, an antibody, targets and kills cancer cells. Venetoclax triggers cancer cell death. Together, these treatments have led to deep remissions, meaning the cancer significantly shrinks or disappears. Although more research is needed specifically for MCL, these findings suggest the combination could be effective. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael Wang, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 have not had any treatment or radiotherapy for my MCL.

My cancer is confirmed as MCL with specific genetic features.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I have a condition that prevents my body from absorbing nutrients properly.

Pregnant or planning pregnancy

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06522386

NCT06522386 | GATE1: A Multicenter Phase II Study of ... GATE1: A Multicenter Phase II Study of Pirtobrutinib, Rituximab and Venetoclax Combination Therapy for Patients With Previously Untreated Mantle Cell Lymphoma.

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0220.html

A multicenter phase II study of pirtobrutinib, rituximab and ... A multicenter phase II study of pirtobrutinib, rituximab and venetoclax combination therapy for patients with previously untreated mantle cell lymphoma.

3. ashpublications.org ashpublications.org/blood/article/145/7/683/534861/High-risk-MCL-recognition-and-treatment

High-risk MCL: recognition and treatment - ASH Publications This article provides a comprehensive update on recognizing and managing high-risk MCL and encompass current practices and future directions.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12288890/

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ... Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open- ...

5. cllsociety.org cllsociety.org/2024/09/combination-pirtobrutinib-venetoclax-and-rituximab-for-cll/

Combination Pirtobrutinib, Venetoclax, and Rituximab for ... The combination of pirtobrutinib, venetoclax, and rituximab was very effective and produced deep remissions in patients with relapsed / refractory CLL.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463717/

Beyond Bruton's tyrosine kinase inhibitors in mantle cell ... A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023;7(13):2983–2993. doi ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124114759

High-risk MCL: recognition and treatment This article provides a comprehensive update on recognizing and managing high-risk MCL and encompass current practices and future directions.