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: 0

Duration: 12 weeks

39 Participants Needed

Trial Summary

What is the purpose of this trial?

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 Cell Lymphoma

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.

What data supports the effectiveness of the drugs Glofitamab and Lenalidomide for treating lymphoma?

Glofitamab has been conditionally approved in Canada for treating certain types of B-cell non-Hodgkin lymphomas, showing promise in patients who have tried other treatments. Lenalidomide, when combined with another drug, has been effective in prolonging the time patients live without their disease getting worse in certain types of non-Hodgkin lymphoma. ^{1 2 3 4 5}

Is the combination of Glofitamab and Lenalidomide safe for humans?

Lenalidomide, also known as Revlimid, has been used in various treatments and is generally considered safe with manageable side effects. Common side effects include fatigue, skin rash, and low blood cell counts, which can be managed with dose adjustments. There is no specific safety data available for the combination of Glofitamab and Lenalidomide, but Lenalidomide alone or with other drugs has shown an acceptable safety profile. ^{2 5 6 7 8}

What makes the drug combination of Glofitamab and Lenalidomide unique for treating lymphoma?

The combination of Glofitamab and Lenalidomide is unique because Glofitamab is a bispecific antibody that recruits T cells to attack tumor cells, while Lenalidomide modifies the immune environment to enhance the activity of immune cells. This dual approach targets lymphoma cells in a novel way compared to traditional treatments. ^{1 2 5 9 10}

Research Team

Anita J Kumar

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]

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

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]

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

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]

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

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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