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)

27 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Glofitamab, Ibrutinib, and Obinutuzumab for Mantle Cell Lymphoma?

Research shows that Ibrutinib, when combined with other drugs like rituximab, has been effective in treating mantle cell lymphoma, improving progression-free survival and achieving significant responses in patients. This suggests that combining Ibrutinib with other drugs, such as Glofitamab and Obinutuzumab, could potentially enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Glofitamab, Ibrutinib, and Obinutuzumab safe for humans?

Ibrutinib, one of the drugs in the combination, has been used in patients with mantle cell lymphoma and chronic lymphocytic leukemia, showing a well-tolerated safety profile. Common side effects include low blood platelet count, diarrhea, low white blood cell count, bruising, and fatigue. While specific safety data for the combination with Glofitamab and Obinutuzumab is not provided, Ibrutinib alone has been generally safe in humans. ^{1 3 4 6 7}

What makes the drug combination of Glofitamab, Ibrutinib, and Obinutuzumab unique for treating mantle cell lymphoma?

This drug combination is unique because it combines Glofitamab, a novel antibody that targets cancer cells, with Ibrutinib, a Bruton's tyrosine kinase inhibitor that disrupts cancer cell growth, and Obinutuzumab, an antibody that helps the immune system attack cancer cells. This multi-faceted approach aims to enhance treatment effectiveness compared to using these drugs individually. ^{1 3 4 5 6}

What is the purpose of this trial?

This phase IB/II trial tests the safety, side effects and effectiveness of glofitamab plus ibrutinib with obinutuzumab for the treatment of patients with mantle cell lymphoma (MCL). Glofitamab is in a class of medications called bispecific monoclonal antibodies. It works by killing cancer cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). In the body, glofitamab binds to a receptor called CD3 on T-cells (a type of immune cells) and a receptor called CD20 on B-cells, a receptor that is often over-expressed on the surface of cancerous B-cells. When glofitamab binds to CD3 and CD20 receptors, it causes an immune response against the CD20-expressing cancerous B-cells. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Glofitamab plus ibrutinib with obinutuzumab may be safe tolerable and/or effective in treating patients with MCL.

Research Team

Stephen E. Spurgeon

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2023]

3. England 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

5. United States 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. [2021]

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

FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia. [2022]