Mosunetuzumab + Lenalidomide vs Rituximab for Follicular Lymphoma

(Celestimo Trial)

Recruiting at 186 trial locations

Overseen By Reference Study ID: GO42909 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Lenalidomide

Must not be taking: Immunosuppressives, Monoclonal antibodies

Disqualifiers: Grade 3b FL, CNS lymphoma, 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: Unknown

Duration: 12 cycles (approximately 9-10 months)

478 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain treatments like systemic immunosuppressive medications within 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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 cannot take certain cancer treatments or immunosuppressive medications shortly before starting the trial. It's best to discuss your specific medications with the study team.

What data supports the idea that Mosunetuzumab + Lenalidomide vs Rituximab for Follicular Lymphoma is an effective treatment?

The available research shows that Lenalidomide combined with Rituximab is an effective treatment for follicular lymphoma. In the AUGMENT trial, this combination significantly delayed the progression of the disease compared to Rituximab alone. Additionally, the RELEVANCE trial found that Lenalidomide with Rituximab was as effective as traditional chemoimmunotherapy, but with different side effects. This suggests that the combination of Lenalidomide and Rituximab is a promising alternative to other treatments for follicular lymphoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination of Mosunetuzumab and Lenalidomide for treating follicular lymphoma?

Research shows that Lenalidomide combined with Rituximab is effective for treating follicular lymphoma, especially in patients whose disease has returned or is resistant to previous treatments. This combination has been shown to improve progression-free survival, which means patients live longer without the disease getting worse. ^{1 2 3 4 5}

What safety data exists for Mosunetuzumab + Lenalidomide vs Rituximab in Follicular Lymphoma?

The safety data for Lenalidomide (Revlimid) in combination with Rituximab (Rituxan) for follicular lymphoma shows that this regimen has an acceptable tolerability profile. Common grade 3/4 adverse events include neutropenia, which is generally manageable with dosage adjustments and growth factor support. Other adverse events include lymphopenia, fatigue, and hyponatremia. Nonhematologic toxicities like fatigue are typically low-grade and manageable with treatment adjustments. Immune-related symptoms such as rash and tumor flare are important to recognize and manage. Venous thromboembolism is uncommon but prophylaxis is recommended. Overall, the combination of Lenalidomide and Rituximab is considered effective and tolerable for patients with relapsed or refractory follicular lymphoma. ^{1 2 5 6 7}

Is the combination of Mosunetuzumab and Lenalidomide safe for treating follicular lymphoma?

Lenalidomide, when combined with rituximab, has shown a manageable safety profile in treating follicular lymphoma. Common side effects include neutropenia (low white blood cell count), which is usually managed with dose adjustments, and other mild symptoms like fatigue. Serious side effects are rare, and the treatment is generally considered safe with proper monitoring. ^{1 2 5 6 7}

Is the drug combination of Lenalidomide, Mosunetuzumab, and Rituximab promising for treating follicular lymphoma?

Yes, the combination of Lenalidomide, Mosunetuzumab, and Rituximab is promising for treating follicular lymphoma. Lenalidomide and Rituximab together have shown to significantly improve progression-free survival in patients with follicular lymphoma. Mosunetuzumab, a new type of treatment, is also proving to be highly effective for patients whose disease has returned or is resistant to other treatments. This combination offers a new and effective option for managing follicular lymphoma. ^{1 2 4 8 9}

What makes the Mosunetuzumab + Lenalidomide vs Rituximab treatment unique for follicular lymphoma?

This treatment is unique because it combines mosunetuzumab, a T-cell-engaging therapy, with lenalidomide and rituximab, offering a novel approach for relapsed or refractory follicular lymphoma. Mosunetuzumab is a bispecific antibody that redirects T-cells to target cancer cells, providing a potent and manageable 'off-the-shelf' option, which is different from traditional chemotherapy-based treatments. ^{1 2 4 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with relapsed or refractory follicular lymphoma who have had at least one prior systemic therapy. They must be in a condition to receive treatment, not have grade 3b FL or transformed indolent disease, and no recent exposure to certain cancer therapies. Participants need adequate organ function and cannot be pregnant, breastfeeding, or planning pregnancy; they must agree to contraception measures.

Inclusion Criteria

My lymphoma is CD20 positive and is grade 1-3a.

I agree to use effective birth control or remain abstinent during and after treatment.

My doctor says I need treatment for my tumor based on its size or specific criteria.

Exclusion Criteria

I have had a solid organ transplant.

I have or had brain lymphoma or cancer spread to the lining of my brain and spinal cord.

I have or might have a long-term active Epstein-Barr virus infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 or rituximab in combination with lenalidomide for 12 cycles

12 cycles (approximately 9-10 months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

US Extension

Non-randomized single arm US extension of mosunetuzumab in combination with lenalidomide

12 cycles (approximately 9-10 months)

Treatment Details

Interventions

• Lenalidomide
• Mosunetuzumab
• Rituximab

Trial Overview The study compares the effectiveness of mosunetuzumab combined with lenalidomide versus rituximab combined with lenalidomide in treating follicular lymphoma. It will assess which combination works better for those who've already tried other treatments.

Participant Groups

Group I: R + Len (Arm B) Experimental Treatment 3 Interventions

Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)

Group II: M + Len (US Extension Arm C) Experimental Treatment 3 Interventions

Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)

Group III: M + Len (Arm A) Experimental Treatment 3 Interventions

Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)

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

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

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]

The combination of lenalidomide and rituximab (LR) showed a significantly higher overall response rate (76%) compared to lenalidomide alone (53%) in patients with recurrent follicular lymphoma, indicating that LR is more effective in treating this condition.

Both treatment regimens had similar rates of severe adverse events (grade 3 to 4), but lenalidomide alone resulted in more treatment failures, suggesting that LR may provide a better balance of efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). Leonard, JP., Jung, SH., Johnson, J., et al.[2022]

Lenalidomide combined with rituximab (LR) has shown superior efficacy compared to either lenalidomide or rituximab alone in treating follicular lymphoma (FL), based on multiple clinical trials.

In a head-to-head comparison with standard chemoimmunotherapy involving 1030 FL patients, LR demonstrated similar efficacy but with a different side effect profile, including myelosuppression, rash, and fatigue, indicating it may be a viable alternative for patients unfit for traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Lenalidomide in Combination with Rituximab for the Treatment of Adult Patients with Follicular Lymphoma: The Evidence to Date. Yilmaz, U., Salihoglu, A., Soysal, T.[2022]

For patients with limited stage follicular lymphoma (FL), treatment options include radiotherapy, watchful waiting, and rituximab, with recent evidence suggesting that rituximab monotherapy may be effective.

In patients with high tumor burdens, combining rituximab with chemotherapy (like R-CHOP or bendamustine) has been shown to improve overall survival, while rituximab maintenance therapy enhances relapse-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Low grade lymphoma: research progress and questions about treatment]. Ishizawa, K.[2015]

Lenalidomide, when used in combination with rituximab, has been shown to be an effective treatment for patients with relapsed or refractory follicular lymphoma, offering a chemotherapy-free option.

This combination therapy improves outcomes compared to using rituximab alone and may serve as a viable alternative to traditional chemoimmunotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[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 II study involving 30 patients with relapsed/refractory indolent non-Hodgkin lymphoma, the combination of lenalidomide and rituximab achieved a high overall response rate of 74%, with 44% of patients experiencing complete responses.

The treatment demonstrated a median progression-free survival of 12.4 months, and while there were some significant adverse events like neutropenia and lymphopenia, the overall toxicity was considered acceptable, indicating a promising safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Tuscano, JM., Dutia, M., Chee, K., et al.[2018]

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]

In a study involving 1030 patients with previously untreated follicular lymphoma, the combination of rituximab and lenalidomide showed similar efficacy to rituximab plus chemotherapy, with complete response rates of 48% and 53% respectively at 120 weeks.

The safety profiles differed between the two treatments, with rituximab-chemotherapy leading to higher rates of severe neutropenia, while rituximab-lenalidomide was associated with more severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. Morschhauser, F., Fowler, NH., Feugier, P., et al.[2021]

References

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

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

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

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]

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

An Overview of Lenalidomide in Combination with Rituximab for the Treatment of Adult Patients with Follicular Lymphoma: The Evidence to Date. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Low grade lymphoma: research progress and questions about treatment]. [2015]

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

Lenalidomide in follicular lymphoma. [2021]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. [2018]

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

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

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

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. [2021]