Glofitamab + Lenalidomide for Lymphoma

Recruiting at 10 trial locations

Overseen By Anita Kumar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: BTK inhibitors

Must not be taking: Anticancer, Immunosuppressive, Corticosteroids, others

Disqualifiers: Active hepatitis, HIV, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining glofitamab (a type of immunotherapy) and lenalidomide can effectively treat mantle cell lymphoma that has returned or resisted other treatments. It targets patients who have tried at least one other treatment without success, specifically those who did not respond to BTK inhibitors. Ideal candidates are individuals with mantle cell lymphoma who haven't responded well to previous treatments and face frequent disease challenges. Participants will help researchers assess whether these two drugs can work together to improve treatment outcomes. 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 new 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, certain treatments like investigational agents, anticancer therapies, and corticosteroids have specific restrictions before starting the study therapy. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

Is there any evidence suggesting that the combination of glofitamab and lenalidomide is likely to be safe for humans?

Research shows that combining glofitamab and lenalidomide may help treat patients with relapsed or refractory Mantle Cell Lymphoma. Previous studies found that glofitamab alone worked well, even for patients who had undergone many treatments. Proper care managed the side effects effectively.

Lenalidomide is often used to treat certain blood cancers, and most people tolerate it well. Like any treatment, it can have side effects, but these are usually manageable with a healthcare team's assistance.

Although detailed information on using these two treatments together is limited, studies on each drug separately in humans provide some reassurance about their safety. This study is in an early phase, focusing on the treatment's safety and tolerability. So far, the data suggests the treatment is promising, but more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Glofitamab and Lenalidomide for treating mantle cell lymphoma because they offer a fresh approach compared to traditional therapies like chemotherapy and BTK inhibitors. Glofitamab is an innovative bispecific antibody that targets both cancer cells and T-cells, effectively bringing the immune system directly to the cancer cells for a more targeted attack. Meanwhile, Lenalidomide enhances the immune system's ability to fight cancer by modifying the body's immune response. Together, these treatments could provide a more effective solution, especially for patients who have not had success with previous treatments.

What evidence suggests that the combination of glofitamab and lenalidomide might be an effective treatment for Mantle Cell Lymphoma?

Research has shown that combining glofitamab and lenalidomide may effectively treat Mantle Cell Lymphoma (MCL) that has returned or not responded to other treatments. In earlier studies, many patients experienced a complete response, meaning their cancer disappeared. Patients who had already tried other therapies received these treatments, and the side effects were manageable with proper care. While glofitamab alone has shown positive results, this trial will test the combination with lenalidomide to determine if it works even better. The current findings are promising, but more research is needed to confirm these early results. ^{1 2 3 5 6}

Who Is on the Research Team?

Anita J Kumar

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with Mantle Cell Lymphoma that has come back or didn't respond to previous treatments. The specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a particular stage of the disease.

Inclusion Criteria

Life expectancy ≥ 12 weeks as determined by patient's primary clinician

My bone marrow and organs are functioning well.

I am willing to undergo additional tests for my disease as required.

Exclusion Criteria

I have had a stem cell transplant.

I do not have any severe illnesses or organ problems.

I haven't had treatment for another cancer within the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glofitamab and lenalidomide for relapsed or refractory Mantle Cell Lymphoma

12 weeks

Regular visits as per treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to receive treatment if deemed beneficial

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Lenalidomide

Trial Overview The study is testing if combining two drugs, Glofitamab and Lenalidomide, can effectively treat Mantle Cell Lymphoma. It might also involve Obinutuzumab as part of the treatment regimen.

How Is the Trial Designed?

Group I: Participants with Mantle Cell Lymphoma Experimental Treatment 3 Interventions

Participants will be diagnosed with relapsed, refractory (R/R) mantle cell lymphoma (MCL) with prior BTK inhibitor (BTKi) failure

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

Glofitamab is a promising new treatment for B cell lymphomas that do not respond to standard R-CHOP chemotherapy, which fails in over one-third of cases.

As a bispecific antibody targeting CD20 and CD3, glofitamab works by engaging T cells to attack tumor cells, offering a novel approach for patients with relapsed or refractory lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. Wang, C., Liu, Y.[2023]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

Glofitamab, a bispecific monoclonal antibody targeting CD20 and CD3, was conditionally approved in Canada on March 25, 2023, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone multiple prior therapies and are ineligible for CAR T-cell therapy.

The drug is currently under regulatory review in the EU and USA, with ongoing clinical development as both a standalone treatment and in combination with other therapies for non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. Shirley, M.[2023]

In a phase 2 study involving 155 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), glofitamab treatment resulted in a complete response in 39% of patients, demonstrating its efficacy as a therapy.

While glofitamab showed promising results, 62% of patients experienced adverse events of grade 3 or higher, with cytokine release syndrome being the most common, affecting 63% of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Dickinson, MJ., Carlo-Stella, C., Morschhauser, F., et al.[2023]

In a phase II trial involving 50 patients with indolent B-cell or mantle cell lymphomas who were previously resistant to rituximab, the combination of lenalidomide and rituximab resulted in a significant increase in overall response rate from 30.2% after lenalidomide alone to 62.8% after adding rituximab.

The median progression-free survival for patients receiving the lenalidomide-rituximab combination was 22.2 months, which was significantly longer than the 9.13 months observed with prior rituximab treatment, indicating that this combination can effectively overcome previous resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Chong, EA., Ahmadi, T., Aqui, NA., et al.[2022]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

Lenalidomide, while effective as a maintenance treatment for mantle-cell lymphoma, can induce rare adverse events such as arthritis, as demonstrated in a case study of a 71-year-old patient who developed scapular-belt arthritis after treatment.

Pharmacovigilance data revealed that arthritis is a rare side effect of lenalidomide, with only three reported cases in France and accounting for just 0.13% of adverse events in the international VigiBase® database, highlighting the need for awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. Icard, C., Mocquot, P., Nogaro, JC., et al.[2022]

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide has shown significant efficacy in improving survival rates for patients with relapsed and refractory myeloma, especially when used alongside other treatments like bortezomib and thalidomide.

While lenalidomide is effective, it is associated with common side effects such as fatigue and thrombocytopenia, and its combination with other agents can increase the risk of blood clots, highlighting the importance of managing these adverse events for continued treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. van de Donk, NW., Görgün, G., Groen, RW., et al.[2021]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06192888?cond=Mantle%20cell%20lymphoma%20OR%20%22classical%20mantle%20cell%20lymphoma%22%20OR%20%22%20LCM%22%20OR%20%22%20mantle%20zone%20lymphoma%22%20OR%20%22%20MCL%22&aggFilters=status:not%20rec&viewType=Table&rank=2

A Study of Glofitamab and Lenalidomide in People ... ... glofitamab and lenalidomide is an effective treatment for relapsed or refractory Mantle Cell Lymphoma. Official Title. Pilot Study of Glofitamab and ...

3. dana-farber.org dana-farber.org/clinical-trials/24-104

Pilot Study of Glofitamab and Lenalidomide in Patients with ... The purpose of this study is to find out whether the combination of glofitamab and lenalidomide is an effective treatment for relapsed or refractory Mantle ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/non-hodgkins-lymphoma/a-study-to-evaluate-glofitamab-as-a-single-agent-vs--in-75996.html

Clinical Trial - Relapsed/Refractory Mantle Cell Lymphoma... This clinical trial aims to compare how well glofitamab works versus standard treatment (BR or R-Len) in people with relapsed/refractory MCL.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12248784/

Next-Generation Therapies in Mantle Cell Lymphoma (MCL) Data on the Glofitamab efficacy in R/R MCL are encouraging; however, follow-up is still limited compared to, for example, with CAR-T, and more mature data ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06084936

NCT06084936 | A Study to Evaluate Glofitamab as a ... The purpose of this study is to evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine ...