Rituximab vs Mosunetuzumab for Follicular Lymphoma

Recruiting at 228 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Uncontrolled diabetes, Hypertension, Active infection, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 16-40 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which treatment is more effective for people with follicular lymphoma, a type of blood cancer, who have a low tumor burden (smaller or fewer tumors). It compares two treatments: rituximab, which helps the immune system attack cancer cells, and mosunetuzumab (also known as Lunsumio), which may prevent cancer cells from growing and spreading. Individuals diagnosed with follicular lymphoma, who have smaller tumors, and feel their disease is causing distress or prefer active management over waiting, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.

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

Previous studies have shown that rituximab is generally well-tolerated. Most patients using rituximab for similar conditions did not experience severe side effects. It targets a protein on certain white blood cells, aiding the immune system in attacking cancer cells.

Research has shown that mosunetuzumab is also usually well-tolerated. In studies, patients with a type of blood cancer handled the treatment without many serious issues. Mosunetuzumab is a newer treatment that helps stop cancer cells from growing and spreading.

Both rituximab and mosunetuzumab have demonstrated good safety records in these studies. While minor side effects can occur, serious problems are uncommon. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for follicular lymphoma, which often includes treatments like Rituximab, Mosunetuzumab offers a novel approach by engaging the body's own immune system in a unique way. Mosunetuzumab is a bispecific antibody that targets both the cancerous B cells and the T cells, potentially enhancing the immune response against the cancer. This dual-targeting mechanism is different from traditional treatments and could lead to more effective and faster results. Researchers are excited about Mosunetuzumab because it offers a promising new way to treat follicular lymphoma with potentially fewer side effects and improved outcomes.

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

This trial will compare Rituximab and Mosunetuzumab for treating follicular lymphoma. Research has shown that Rituximab, which participants in this trial may receive, effectively treats follicular lymphoma. In one study, 51.1% of patients experienced no cancer progression after 10 years with Rituximab, compared to 35% who received no treatment. Another study found that patients using Rituximab had a survival rate of 80-83% over 10 years.

Mosunetuzumab, another treatment option in this trial, has also shown promising results in early research. About 60% of patients maintained their response to treatment for 18 months, and 82.4% were still alive at 36 months. Comparatively, Mosunetuzumab had an overall response rate of 80%, slightly better than similar treatments. ^{1 2 4 5 6}

Who Is on the Research Team?

Nilanjan Ghosh

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for people with a confirmed diagnosis of classic follicular lymphoma without 'blastoid' features or grade 3B. They should have a low tumor burden, meaning no more than 3 large tumors and none bigger than 7 cm. Participants must not have severe symptoms, spleen enlargement, organ compression issues, or fluid buildup due to the cancer.

Inclusion Criteria

Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration)

My follicular lymphoma has specific genetic features and lacks common mutations.

Participants must not have a positive test result for COVID-19 within seven (7) days prior to registration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rituximab or mosunetuzumab. Rituximab is administered intravenously and subcutaneously, while mosunetuzumab is administered subcutaneously.

16-40 weeks

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for 5 years and then yearly for a total of 10 years.

10 years

Biannual visits for the first 5 years, then annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Rituximab

Trial Overview The trial compares rituximab (a monoclonal antibody targeting CD20 on B cells) with mosunetuzumab (another monoclonal antibody that may stop cancer cells from growing). It's unclear which treatment is better for patients with low tumor burden follicular lymphoma.

How Is the Trial Designed?

Group I: Arm II (Mosunetuzumab) Experimental Treatment 4 Interventions

Patients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET/CT and blood sample collection on study and during follow up.

Group II: Arm I (Rituximab, rituximab and hyaluronidase) Experimental Treatment 5 Interventions

Patients receive rituximab IV on day 1 of cycle 1 and receive rituximab and hyaluronidase SC on days 8, 15 and 22 of cycle 1 and SC on day 1 of subsequent cycles. Cycles repeat every 56 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET/CT and blood sample collection on study and during follow up.

Mosunetuzumab is already approved in European Union, United States for the following indications:

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 83 patients with Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, switching between the reference rituximab and its biosimilars (TRUXIMA and RIXATHON) did not lead to any new safety concerns, with adverse events being similar to those reported in existing literature.

Out of 465 rituximab infusions, 84.5% of patients experienced at least one adverse event, but only 5.9% had serious grade 3-4 events, indicating that the biosimilars are as safe as the reference product when switching is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of switching between rituximab biosimilars in onco-hematology. Urru, SAM., Spila Alegiani, S., Guella, A., et al.[2021]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

Rituximab is effective in treating both newly diagnosed and relapsed or refractory follicular lymphoma, whether used alone or with chemotherapy.

Due to its good tolerability, rituximab is being explored for maintenance therapy to enhance progression-free and overall survival in patients with follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of postremission therapy in follicular lymphoma: efficacy of rituximab maintenance. Roy, R., Gordon, LI.[2019]

Rituximab has been shown to significantly improve progression-free and overall survival in patients with various types of non-Hodgkin lymphoma and chronic lymphocytic leukaemia (CLL), based on a systematic review of 56 randomized controlled trials.

The consensus guidelines recommend rituximab for use in combination with chemotherapy for initial treatment of aggressive B-cell lymphomas, maintenance therapy for indolent B-cell lymphomas, and as part of treatment regimens for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. Prica, A., Baldassarre, F., Hicks, LK., et al.[2018]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials.

The treatment is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for various lymphoma types, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. Keating, GM.[2021]

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., et al.[2023]

Rituximab has significantly improved survival rates in patients with non-Hodgkin lymphomas, but there is a lack of comprehensive data on its long-term safety, indicating a need for extended patient follow-up.

Current literature provides limited guidance on systematic follow-up models for patients receiving rituximab, highlighting the necessity for developing monitoring strategies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? Hegele, V., Stoll, P., Wüst, D., et al.[2021]

Mosunetuzumab, a T-cell-dependent bispecific antibody, is the first approved treatment for relapsed and refractory follicular lymphoma (FL), showing high efficacy and manageable side effects.

The review highlights the evolving treatment landscape for FL, emphasizing the potential of T-cell-redirecting therapies to improve outcomes for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma. Matarasso, S., Assouline, S.[2023]

Rituximab is an effective treatment for follicular lymphoma (FL), improving outcomes when used in combination with traditional chemotherapy, and has shown significant benefits as a maintenance therapy without increasing side effects or compromising patients' quality of life.

Despite its long history of use, new safety alerts and side effects have emerged that clinicians need to be aware of, highlighting the importance of ongoing monitoring and management in patients receiving rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. Aguiar-Bujanda, D., Blanco-Sánchez, MJ., Hernández-Sosa, M., et al.[2022]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/7/708/525779/Long-term-3-year-follow-up-of-mosunetuzumab-in

Long-term 3-year follow-up of mosunetuzumab in relapsed or ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

2. lunsumio-hcp.com lunsumio-hcp.com/efficacy/clinical-trial-results.html

LUNSUMIO™ (mosunetuzumab-axgb) Efficacy | HCP ~6 out of 10 patients who achieved an overall response maintained response at 18 months. ... 7 out of 10 patients who achieved complete response maintained ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37840271/

Comparative effectiveness between mosunetuzumab ... Overall response and complete response rates were 80% and 60% in the mosunetuzumab cohort and 75% and 33% in the RWD cohort, odds ratios of 1.23 ...

4. lunsumio.com lunsumio.com/results/clinical-trial-results.html

Clinical trial results This study was a phase 2 clinical trial, meaning it studied an investigational treatment to test how well it worked and monitored for potential side effects ...

5. hematologyadvisor.com hematologyadvisor.com/news/follicular-lymphoma-mosunetuzumab-durable-responses-treatment-risk/

Mosunetuzumab Shows Durable Responses in Follicular ... Overall, the median PFS was 24.0 months. The median OS was not yet reached, and 82.4% of patients were alive at 36 months. The median time to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35803286/

Safety and efficacy of mosunetuzumab, a bispecific ... In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to ...