Mosunetuzumab + Lenalidomide vs Rituximab for Follicular Lymphoma

(Celestimo Trial)

Recruiting at 219 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two treatments for individuals with follicular lymphoma, a type of blood cancer that has returned or not responded to previous treatment. One group will receive mosunetuzumab (Lunsumio) and lenalidomide (Revlimid), while the other will receive rituximab and lenalidomide. The goal is to determine which combination is more effective and safer. Individuals who have previously undergone treatment for follicular lymphoma and still require further therapy may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants with access to potentially effective treatments.

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.

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

Research has shown that the combination of mosunetuzumab and lenalidomide is generally safe, with most people tolerating the side effects. Patients with relapsed or hard-to-treat follicular lymphoma have experienced promising results, including lasting improvements and better survival rates.

Similarly, the combination of rituximab and lenalidomide has been well-researched and proven safe and effective for individuals with follicular lymphoma. This treatment helps patients remain in remission longer, keeping their cancer inactive.

Both treatments have undergone extensive testing on many patients before reaching this trial stage, indicating relative safety. While side effects can occur, past studies have shown they are usually manageable. These findings may reassure those considering joining a trial about the safety of the treatments being tested. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard follicular lymphoma treatments that primarily involve chemotherapy and rituximab, mosunetuzumab and lenalidomide offer a novel approach. Mosunetuzumab is a bispecific antibody that uniquely targets both CD20 on B-cells and CD3 on T-cells, effectively recruiting the body's immune system to attack cancer cells. Lenalidomide, an immunomodulatory drug, enhances the immune response, making these combinations potentially more effective. Researchers are excited because these treatments could offer a less toxic and more targeted option, potentially leading to better outcomes for patients.

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

This trial will compare two treatment combinations for relapsed or refractory follicular lymphoma. Participants in one arm will receive mosunetuzumab and lenalidomide, a combination that previous studies have shown to lead to long-lasting remissions and improved survival, with about 60% of patients experiencing a complete response. This suggests it can effectively target lymphoma cells and help patients achieve significant remission. Meanwhile, participants in another arm will receive rituximab and lenalidomide, which past research has also found successful, with a complete response rate of up to 55% in similar patient groups. Both combinations are being tested for their potential to improve outcomes for people dealing with this type of lymphoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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, 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]

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]

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]

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025024516

IBCL-1256: Mosunetuzumab in Relapsed/Refractory ... In mosunetuzumab monotherapy trials, the overall response rates (ORRs) were 80%, 68%, 78.9%, and 74%, and the complete response (CR) rates were 60%, 50%, 68.4%, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04246086

NCT04246086 | A Study Evaluating the Safety, ... This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430742/

P1125: CELESTIMO: A PHASE III TRIAL EVALUATING ... A randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of M-Len versus rituximab plus Len (R-Len) in patients with previously ...

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1644/528990/Mosunetuzumab-with-Response-Driven-Lenalidomide

Mosunetuzumab with Response-Driven Lenalidomide ... In that setting, Mosun provides 60% complete response (CR) rate despite prior immunosuppressive therapy [Budde et al., Lancet Oncol 2022].

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121021261

Mosunetuzumab in Combination with Lenalidomide Has a ... Mosunetuzumab in Combination with Lenalidomide Has a Manageable Safety Profile and Encouraging Activity in Patients with Relapsed/Refractory Follicular Lymphoma ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/non-hodgkins-lymphoma/a-study-evaluating-the-safety--pharmacokinetics--and-ef-94381.html

Clinical Trial - Follicular Lymphoma - mosunetuzumab plus... Study evaluating the safety, pharmacokinetics, and efficacy of mosunetuzumab plus lenalidomide in patients with follicular lymphoma.

8. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper174432.html

Paper: Preliminary Findings of a Phase Ib/II Trial Indicate ... We present preliminary safety, efficacy, and biomarker data from this ongoing trial of M (subcutaneous [SC]) combined with oral Len in pts with 1L FL who ...