Glofitamab + Ibrutinib + Obinutuzumab for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: Cardiovascular disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12-17 cycles (each cycle is 21 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a combination of three drugs—glofitamab, ibrutinib, and obinutuzumab—for treating mantle cell lymphoma (MCL), a type of cancer. These drugs work together to target and destroy cancer cells. The trial aims to determine how well this combination can slow or stop the spread of MCL. Individuals with pathologically confirmed MCL, who have not received prior treatments for this condition, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you may need to modify or stop certain medications, especially if they interact with the trial drugs. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of glofitamab, ibrutinib, and obinutuzumab is generally safe for patients with relapsed or refractory mantle cell lymphoma (MCL). In studies involving patients with multiple prior treatments, glofitamab was well-tolerated when administered for a set period, with manageable side effects given the right support.

Ibrutinib, already approved for other conditions, usually works well by blocking proteins that aid cancer cell growth. Obinutuzumab, like glofitamab, has also demonstrated safety in other treatments. Although the combination is still under study, these findings suggest it may be safe for treating MCL. Patients should always consult healthcare professionals about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Glofitamab, Ibrutinib, and Obinutuzumab for treating Mantle Cell Lymphoma because it offers a novel approach with promising mechanisms of action. Glofitamab is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells, potentially enhancing the immune system's ability to fight lymphoma. Ibrutinib is a Bruton's tyrosine kinase inhibitor, which can disrupt cancer cell survival signals, and Obinutuzumab is an anti-CD20 monoclonal antibody that helps attack cancer cells directly. This multi-pronged strategy could improve outcomes compared to standard treatments, which typically involve chemotherapy and single-agent therapies.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

In this trial, participants will receive a combination of glofitamab, ibrutinib, and obinutuzumab to treat mantle cell lymphoma (MCL). Studies have shown that these three drugs together can be effective. Glofitamab is a medicine that helps the immune system attack cancer by targeting both T-cells and cancerous B-cells. In past research, some patients with MCL that returned or didn't respond to other treatments saw their cancer disappear after using glofitamab. Ibrutinib stops cancer cells from growing and has helped MCL patients in other studies. Obinutuzumab interferes with cancer cell growth. Together, these treatments might offer a strong way to fight MCL. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen E. Spurgeon

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with Mantle Cell Lymphoma. It's designed to test the safety and effectiveness of a combination treatment involving glofitamab, ibrutinib, and obinutuzumab. Participants should meet specific health criteria but those details are not provided here.

Inclusion Criteria

My Mantle Cell Lymphoma (MCL) diagnosis is confirmed with specific genetic markers.

ALT and AST ≤ 3 × upper limit of normal (ULN)

Undetectable hepatitis C virus (HCV) antigen serology. Confirmed by PCR for HCV ribonucleic acid (RNA) if results are disputable

Exclusion Criteria

I have never had progressive multifocal leukoencephalopathy or cancer affecting my brain.

I haven't had any serious infections or been hospitalized for them in the last month.

Concurrent participation in another therapeutic clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ibrutinib orally once daily on days 1-21 of cycles 1-17, glofitamab intravenously on days 8 and 15 of cycle 2 and then on day 1 of cycles 3-13, and obinutuzumab intravenously on cycle 2 day 1 and 2. Cycles repeat every 21 days.

12-17 cycles (each cycle is 21 days)

Multiple visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for up to 2 years.

Up to 2 years

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Ibrutinib
• Obinutuzumab

Trial Overview The study examines a new therapy combining glofitamab (a bispecific monoclonal antibody), ibrutinib (a kinase inhibitor), and obinutuzumab (another monoclonal antibody) in treating MCL. The trial will assess if this combo is safe, tolerable, and effective against cancer cells.

How Is the Trial Designed?

Group I: Treatment (glofitamab, ibrutinib, obinutuzumab) Experimental Treatment 9 Interventions

Patients receive ibrutinib PO QD on days 1-21 of cycles 1-17. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients receive glofitamab IV over 2-4 hours on days 8 and 15 of cycle 2 and then on day 1 of cycles 3-13. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab IV over 4 hours on cycle 2 day 1 and 2. Additionally, patients undergo echocardiography during screening, bone marrow biopsy on study, and CT scans, FDG PET/CT scans or MRI, and blood sample collection throughout the study.

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

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

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

Published Research Related to This Trial

In a phase 2 trial involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib, lenalidomide, and rituximab resulted in a high overall response rate of 76%, with 56% achieving a complete response, suggesting this triplet therapy is effective.

While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment-related deaths, highlighting the need for careful monitoring and further evaluation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Jerkeman, M., Eskelund, CW., Hutchings, M., et al.[2022]

In a phase 2 study involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib and rituximab resulted in an impressive 88% objective response rate, with 44% of patients achieving a complete response.

The treatment was generally well tolerated, with the most common serious side effect being atrial fibrillation in 12% of patients, indicating that while effective, monitoring for cardiac issues is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Wang, ML., Lee, H., Chuang, H., et al.[2021]

In a phase II study involving 50 previously untreated patients with indolent mantle cell lymphoma (MCL), the combination of ibrutinib and rituximab resulted in an impressive 80% complete response rate after 12 treatment cycles.

The treatment also led to undetectable minimal residual disease (MRD) in 87% of patients, allowing 69% of evaluable patients to safely discontinue ibrutinib after 2 years, although caution is advised for those with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Giné, E., de la Cruz, F., Jiménez Ubieto, A., et al.[2022]

In a network meta-analysis of three randomized controlled trials involving 1459 patients with newly diagnosed mantle-cell lymphoma (MCL) ineligible for intensive therapy, the combination of ibrutinib plus bendamustine and rituximab (Ibru + BR) significantly improved progression-free survival (PFS) compared to other regimens like VR-CAP and R-CHOP.

Ibru + BR had a 94.9% probability of being the best treatment option for prolonging PFS, with no significant differences in adverse events compared to the other treatment regimens, indicating its efficacy and safety for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Sheng, Z., Wang, L.[2023]

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

Bruton's tyrosine kinase inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective and well-tolerated treatment options for patients with mantle cell lymphoma who have already undergone one line of therapy.

These inhibitors offer a promising alternative for patients who experience relapse or drug resistance after initial chemo-immunotherapy, highlighting the need for novel treatment strategies in this aggressive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. Hanna, KS., Campbell, M., Husak, A., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06357676

Study Details | NCT06357676 | Glofitamab Plus Ibrutinib ... This phase IB/II trial tests the safety, side effects and effectiveness of glofitamab plus ibrutinib with obinutuzumab for the treatment of patients with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02470

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39365960/

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

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

High-risk MCL: recognition and treatment - ASH Publications Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124044045

5-y Follow-up of Combination of Ibrutinib, Obinutuzumab ... Targeted therapies (such as Ibrutinib and Venetoclax) have improved Mantle Cell Lymphoma (MCL) patients' outcomes. OAsIs trial has evaluated the ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/glofitamab?pn=1

Clinical Trials Using Glofitamab - NCI Glofitamab Plus Ibrutinib with Obinutuzumab for the Treatment of Patients with Mantle Cell Lymphoma. Status: Active. Location: OHSU Knight Cancer Institute ...