Rituximab vs Mosunetuzumab for Follicular Lymphoma

Recruiting at 158 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Uncontrolled diabetes, Hypertension, Active infection, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effectiveness of rituximab to mosunetuzumab in treating patients with follicular lymphoma with a low tumor burden. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. It is not yet known if giving rituximab or mosunetuzumab works better in treating patients with follicular lymphoma with a low tumor burden.

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.

What data supports the effectiveness of the drugs Rituximab and Mosunetuzumab for treating follicular lymphoma?

Mosunetuzumab has been conditionally approved in the EU for adults with follicular lymphoma who have tried at least two other treatments, showing it can be effective for this condition. Rituximab, when added to chemotherapy, has been shown to improve outcomes in patients with follicular lymphoma, making it a valuable treatment option. ^{1 2 3 4 5}

What is known about the safety of Rituximab and Mosunetuzumab for human use?

Rituximab has been used for over two decades and is generally considered safe, with some patients experiencing mild to moderate side effects. Mosunetuzumab has been conditionally approved in the EU for certain lymphoma cases, indicating it has passed safety evaluations for human use, though specific side effects are not detailed in the provided research. ^{1 6 7 8 9}

How does the drug Mosunetuzumab differ from other treatments for follicular lymphoma?

Mosunetuzumab is unique because it is a T-cell-engaging bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells, helping the immune system attack cancer cells. Unlike traditional treatments, it offers an 'off-the-shelf' option with manageable side effects for patients with relapsed or refractory follicular lymphoma. ^{1 2 3 5 10}

Research Team

Nilanjan Ghosh

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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.

I do not have an active autoimmune disease that needs treatment.

Trial Timeline

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

Treatment Details

Interventions

• Mosunetuzumab (Monoclonal Antibodies)
• Rituximab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

References

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

Mosunetuzumab: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand 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. [2021]

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

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

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

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. [2018]

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

Safety of switching between rituximab biosimilars in onco-hematology. [2021]

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

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. [2022]

8. United States 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. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]

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

Optimization of postremission therapy in follicular lymphoma: efficacy of rituximab maintenance. [2019]