Mosunetuzumab + Lenalidomide vs Rituximab for Follicular Lymphoma
(Celestimo Trial)
Recruiting in Palo Alto (17 mi)
+185 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Hoffmann-La Roche
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
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.
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.
12345What 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.
12567Is 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.
12489Eligibility 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.
+6 more
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.
+28 more
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: R + Len (Arm B)Experimental Treatment3 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 Treatment3 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 Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Aurora St. Luke's Medical CenterMilwaukee, WI
Wake Forest University Baptist Medical Center; Comprehensive Cancer Center, 3rd FloorWinston-Salem, NC
Investigative Clinical Research of Indiana, LLCNoblesville, IN
Advocate Medical Group - Park Ridge, Luther Lane - OncologyPark Ridge, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Hoffmann-La RocheLead Sponsor
References
Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]Lenalidomide (Revlimid®) is a targeted immunomodulatory drug with multiple mechanisms of action. In the USA and the EU, oral lenalidomide is indicated in combination with rituximab or a rituximab product for the treatment of patients with previously treated follicular lymphoma. In the pivotal, phase III AUGMENT trial, lenalidomide + rituximab significantly prolonged progression-free survival (PFS; primary endpoint) relative to placebo + rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma, with the PFS benefit appearing to be specific to patients with follicular lymphoma and extending to elderly patients with this subtype. Lenalidomide + rituximab also demonstrated activity in an interim analysis of the phase III MAGNIFY trial in patients with relapsed or refractory indolent non-Hodgkin lymphoma, including those with rituximab-refractory disease. Lenalidomide had an acceptable tolerability profile. Although grade 3 or 4 neutropenia occurred more frequently with lenalidomide + rituximab than with placebo + rituximab, this was generally well managed with dosage adjustments and growth factor support. In conclusion, lenalidomide in combination with rituximab represents an important new treatment option for previously treated follicular lymphoma, including patients whose disease has become refractory to rituximab.
Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.
An Overview of Lenalidomide in Combination with Rituximab for the Treatment of Adult Patients with Follicular Lymphoma: The Evidence to Date. [2022]Follicular lymphoma (FL) is an indolent (low-grade) malignancy of B cells and is among the most common hematological cancers affecting adults. Its clinical presentation, natural course, and severity are highly variable. Management of FL depends on the clinical setting; most patients require multiple lines of treatment. Chemoimmunotherapy is the standard of care for FL patients needing treatment; however, alternative treatments are limited for refractory patients or those unfit for chemoimmunotherapy. Multiple alternatives to chemoimmunotherapy for FL are being developed, with some showing significant promise. Lenalidomide combination with rituximab (LR) is among the most successful and extensively studied novel approaches. LR has been compared head-to-head in clinical trials with rituximab monotherapy and chemoimmunotherapy in the frontline and to lenalidomide or rituximab monotherapy in the relapsed or refractory setting for the treatment of FL. Initial reports of these nine trials have been published in the last decade, and their long-term data will be available in the coming years. LR offered superior efficacy to either lenalidomide or rituximab monotherapy alone. The RELEVANCE trial compared the efficacy of LR with chemoimmunotherapy among 1030 FL patients and demonstrated similar efficacy with a different side effect profile. Myelosuppression, rash, and fatigue were among the significant adverse events. Most patients treated with LR received thromboprophylaxis. This paper aims to summarize and comment on the published evidence regarding LR treatment for FL through a literature review. The clinical trials will be presented in detail, and methodological differences complicating their comparisons will be discussed.
[Low grade lymphoma: research progress and questions about treatment]. [2015]Treatment options for follicular lymphoma (FL) are considered when patients have limited stage, low tumor burden advanced stage, and high tumor burden advanced stage disease. Although patients with limited stage FL are managed with radiotherapy (24-36 Gy), watchful waiting (WW), rituximab monotherapy, and rituximab combined with chemotherapy need to be evaluated. In patients with low tumor burdens, WW is regarded as the standard management. The usefulness of rituximab monotherapy was also recently suggested. Rituximab combined with chemotherapy improved overall survival (OS) in patients with high tumor burdens and the optimal reference regimen might be R-CHOP or rituximab combined with bendamustine. As to efficacy, improved relapse-free survival, with rituximab maintenance, has been shown. In patients with primary macroglobulinemia, fludarabine improved both progression-free survival and OS as compared with chlorambucil. As to extra-nodal marginal-zone B cell lymphoma, the addition of rituximab to chlorambucil improves both the response rate and event-free survival. Large clinical trials of lenalidomide, idelalisib, and ibrutinib are now ongoing.
Lenalidomide in follicular lymphoma. [2021]Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.
Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.
Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. [2018]This phase II study evaluated the safety and efficacy of lenalidomide in combination with rituximab in patients with relapsed/refractory, indolent non-Hodgkin lymphoma (NHL). Patients were treated with daily lenalidomide in 28-d cycles and weekly rituximab for 4 weeks. Lenalidomide was continued until progression or unacceptable toxicity. Twenty-two patients were assessed for FCGR3A polymorphisms. Thirty patients were enrolled; 27 were evaluable for response. The overall response rate (ORR) was 74% including 44% complete responses (CR); median progression-free survival (PFS) was 12·4 months. The 13 rituximab refractory patients had an ORR of 61·5% (four CR/unconfirmed CR). The ORR was 77% in the 22 follicular lymphoma patients (nine CR/unconfirmed CR). At a median follow-up time of 43 months, the median duration of response and time to next therapy were 15·4 and 37·4 months, respectively. Most common grade 3/4 adverse events were lymphopenia (45%), neutropenia (55%), fatigue (23%) and hyponatraemia (9%). The ORR and PFS in patients with low-affinity FCGR3A polymorphisms (F/F and F/V) suggest that lenalidomide may improve the activity of rituximab in these patients. These data suggest that combining lenalidomide with rituximab can produce durable responses with acceptable toxicity in patients with indolent NHL.
Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma. [2023]Follicular lymphoma (FL) is the most common indolent lymphoma. Since the advent of rituximab, FL has seen a progressive improvement in patient prognosis. While chemotherapy combined with an anti-CD20 monoclonal antibody remains standard first-line therapy, most patients will relapse and require subsequent therapy. T-cell-redirecting therapies can be very potent and are transforming the therapeutic landscape in the relapsed and refractory (R/R) setting. T-cell-dependent bispecific antibodies, of which mosunetuzumab is the first to be approved for R/R FL, are proving to be a highly effective, 'off-the-shelf' option with manageable toxicities. This review covers approved treatments for R/R FL and focuses on preclinical and clinical data available for mosunetuzumab (Lunsumio™), with the goal of determining its role in the treatment of R/R FL.
Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. [2021]Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.