Odronextamab vs Chemotherapy for Follicular Lymphoma

(OLYMPIA-1 Trial)

Recruiting in Palo Alto (17 mi)

+284 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Systemic anti-lymphoma

Disqualifiers: CNS lymphoma, High-grade transformation, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma (a type of non-Hodgkin lymphoma or NHL). This study will be made up of two parts: Part 1 (non-randomized) and Part 2 (randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when given alone. The aim of Part 2 of the study is to see how the study drug works compared to rituximab (called the "comparator drug") and chemotherapy (the current standard of care for NHL). Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) * How the study drug affects quality of life and ability to complete routine daily activities.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had any systemic anti-lymphoma therapy, which might imply stopping certain treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Odronextamab compared to chemotherapy for follicular lymphoma?

Research shows that the combination of bendamustine and rituximab (R-B) is an effective treatment for follicular lymphoma, achieving similar response rates to the standard R-CHOP regimen, with a better complete remission rate. This suggests that bendamustine, a component of the chemotherapy regimen, is effective in treating follicular lymphoma.

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Is the treatment with Odronextamab and chemotherapy safe for humans?

Bendamustine, often used with rituximab for treating follicular lymphoma, has been studied for safety. Some studies show it has an acceptable safety profile, but there have been reports of serious side effects, including a 2.5% rate of fatal adverse events in some cases.

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What makes the drug Odronextamab unique for treating follicular lymphoma?

Odronextamab is a novel treatment option for follicular lymphoma that differs from traditional chemotherapy regimens like R-CHOP or R-B (rituximab plus bendamustine) by potentially offering a different mechanism of action, as it is a bispecific antibody designed to engage T-cells to target and kill cancer cells. This approach may provide an alternative for patients who do not respond well to standard chemotherapy treatments.

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Eligibility Criteria

This trial is for adults with a type of non-Hodgkin lymphoma called follicular lymphoma, who haven't been treated before. They should have a certain level of physical fitness (ECOG 0-2) and their bone marrow and liver must be functioning well. People with CNS involvement, transformed high-grade lymphomas, or specific other conditions are excluded.

Inclusion Criteria

You need the specific treatment described in the study protocol.

My cancer can be measured on a CT or MRI scan.

My liver and bone marrow are working well.

Exclusion Criteria

My cancer is in the brain or spinal cord.

You have an infection or you are allergic to the study drug or any of its ingredients.

I am currently receiving or have received systemic therapy for lymphoma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety Run-in

Participants receive odronextamab to assess safety and tolerability

Up to 30 months

Part 2: Randomized Controlled

Participants are randomized to receive either odronextamab or rituximab with chemotherapy

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Participant Groups

The study tests odronextamab against the usual treatment combination of rituximab and chemotherapy for follicular lymphoma. It has two parts: first to check safety and tolerability, then to compare effectiveness. The study also looks at how much drug is in the blood over time, potential antibodies against it, side effects, and life quality impacts.

Group I: Odronextamab Experimental Treatment 1 Intervention

Part 1 is a safety run-in. All participants will receive odronextamab. In part 2 participants will be randomly assigned in a 1:1 ratio to receive odronextamab followed by odronextamab maintenance.

Group II: Rituximab + Investigator's Choice Chemotherapy Active Control 6 Interventions

Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

🇪🇺 Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

🇨🇦 Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

🇯🇵 Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center Orange, CA

Cisss de la Monteregie-Centre Greenfield Park, Canada

CHU de Quebec - Universite Laval Quebec City, Canada

Beth Israel Deaconess Medical Center Boston, MA

More Trial Locations

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals Lead Sponsor

References

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

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. [2022] One key clinical challenge remains in how to sequence treatments in follicular lymphoma (FL). The chemoimmunotherapy rituximab cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (R-CHOP) has been a standard treatment option for two decades. However, there are limited data to suggest in which line R-CHOP should be used for older patients.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of first-line treatment with bendamustine plus rituximab versus R-CHOP for patients with follicular lymphoma grade 3A: Results of a retrospective study from the Fondazione Italiana Linfomi. [2023] In the setting of follicular lymphoma (FL), frontline therapy with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) has represented for many years the standard of care for patients with symptomatic advanced disease. More recently, the combination of bendamustine plus rituximab (R-B) has emerged as an alternative therapeutic option. We present a retrospective, multicenter, observational study aimed at comparing outcomes and toxicities observed in 145 patients diagnosed with grade 3A FL treated with a first line therapy in 15 Italian Fondazione Italiana Linfomi centers between the 1st of January 2014 and the 30th of May 2018. Seventy patients were treated with R-B and 75 with R-CHOP. In the R-B group, the median age at the time of diagnosis was 67 years compared with 59 years in the R-CHOP group. Patients in R-B group achieved a similar overall response rate (96% vs. 99%) and a better complete remission rate (87% vs. 80%, p=0.035) compared with patients in R-CHOP group. Progression free survival (PFS) was similar between individual treated with R-CHOP and R-B (48- month PFS 77.7% vs. 76.6% respectively, p=0.745). The overall survival was significantly longer with R-CHOP treatment (HR=0.16; 95% IC, 0.04-0.74; p=0.007); however, no statistical significant difference was observed after adjustment for age. With the limitations of the study design, our results suggest that both R-B and R-CHOP seem to be valid first-line treatment options in FL3A.

3. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. [2019] Rituximab plus bendamustine (R-B) has been demonstrated to improve outcomes and reduce toxicity compared with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) in follicular lymphoma (FL). Nevertheless, in clinical practice, many centers still prefer R-CHOP to R-B in patients with FL grade 3A (FL3A). Therefore, we retrospectively assessed patients with FL3A treated with either R-CHOP or R-B in five European cancer centers and compared their outcomes.

4. Italy pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study. [2023] Follicular lymphoma (FL) is the most common type of indolent non-Hodgkin lymphoma. Despite treatment advances that have improved outcomes for patients with relapsed or refractory (R/R) FL, many patients still die from progressive disease or treatment-related toxicities. In the phase Ib/II GO29365 study (NCT02257567), the safety and efficacy of polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) versus BR alone, and polatuzumab vedotin plus bendamustine and obinutuzumab (Pola-BG) as a single-arm cohort were evaluated in patients with R/R FL. Following the phase Ib safety run-in, patients were randomized 1:1 to receive Pola-BR or BR alone in the phase II stage; a separate non-randomized Pola-BG cohort was examined in the phase Ib/II expansion stage. Primary endpoints included safety and tolerability (phase Ib) and positron emission tomography complete response (PET-CR) rate by independent review committee (phase II). Overall, 112 patients were enrolled (phase Ib safety run-in: Pola-BR, n=6; phase II randomized cohort: Pola-BR, n=39; BR, n=41; phase Ib/II expansion cohort: Pola-BG, n=26). PET-CR rates were 66.7% (phase Ib safety run in, Pola-BR); 69.2% (phase II randomized, Pola-BR); 63.4% (phase II randomized, BR); and 65.4% (phase Ib/II expansion Pola-BG). There was a higher occurrence of cytopenias with Pola-BR and Pola-BG than with BR; serious adverse events were more frequent with Pola-BR (61.4%) and Pola-BG (46.2%) than with BR (29.3%). Overall, this analysis does not demonstrate a benefit of adding Pola to BR or BG regimens for patients with R/R FL.

5. Switzerland pubmed.ncbi.nlm.nih.gov

Ongoing trials in low-grade lymphoma. [2021] There are many therapies available for the management of low-grade lymphoma. With follicular lymphoma, for example, combination of chemotherapy and rituximab (immuno-chemotherapy) and consecutive maintenance therapy for 2 years is the current standard of care. To date, the most widely used regimen seems to be rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Substitution of liposomal doxorubicin in place of conventional doxorubicin may improve outcomes in this indication, although evidence for its use in low-grade lymphoma is not as relevant as in aggressive lymphoma. Bendamustine, in combination with rituximab, has shown very good efficacy and tolerability in several lymphoma types, particularly follicular lymphoma and other low-grade lymphomas. Other combinations, such as those including bortezomib and lenalidomide, are under investigation in low-grade lymphoma, and the duration of rituximab maintenance therapy following bendamustine-rituximab-containing induction is being researched by the German Study Group for Indolent Lymphoma (StiL).

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

Bendamustine in the treatment of non-Hodgkin's lymphomas. [2021] To review available data using bendamustine alone and in combination with other chemotherapeutic agents in treatment of patients with non-Hodgkin's lymphomas.

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

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. [2020] The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment.

8. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022] We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey.

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma]. [2023] To investigate the clinical efficacy and safety of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with lymphoma.

10. England pubmed.ncbi.nlm.nih.gov

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. [2020] Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

11. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. [2022] Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas.