Odronextamab + Chemotherapy for Follicular Lymphoma

(OLYMPIA-2 Trial)

Recruiting at135 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: CNS lymphoma, High-grade lymphoma, Others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called odronextamab combined with chemotherapy for people with a type of blood cancer called follicular lymphoma. It aims to find out how safe and effective this combination is, especially for those who haven't been treated before or whose cancer came back or didn't respond to previous treatments. The study will also compare this new treatment to the current standard treatment and look at side effects and quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Odronextamab + Chemotherapy for Follicular Lymphoma?

The combination of rituximab with chemotherapy agents like cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been a standard treatment for follicular lymphoma for many years, showing effectiveness in managing the disease. Additionally, rituximab combined with other chemotherapy regimens has demonstrated strong long-term antitumor effects in follicular lymphoma, suggesting that similar combinations, including Odronextamab, may also be effective. ^{1 2 3 4 5}

Is the combination of Odronextamab and chemotherapy safe for humans?

The combination of rituximab with chemotherapy drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone has been studied in various types of lymphoma, showing that it can be safe, though it may cause severe side effects. These treatments are often used with careful monitoring to manage adverse reactions. ^{6 7 8 9 10}

What makes the drug combination of Odronextamab and chemotherapy unique for treating follicular lymphoma?

This treatment is unique because it combines Odronextamab, a newer agent, with a well-established chemotherapy regimen (R-CHOP), potentially offering a novel approach to enhance treatment efficacy for follicular lymphoma, especially in cases where standard treatments may not be as effective. ^{1 3 6 9 11}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

Adults with previously untreated follicular lymphoma can join this trial. They should be able to perform daily activities (ECOG 0-2) and have a certain level of disease severity (FLIPI-1 score). Participants must not have other types of lymphomas, recent major surgeries, organ transplants, or any condition that could risk their safety in the study.

Inclusion Criteria

For Part 1B: previously untreated individuals with a FLIPI-1 score ranging from 3 to 5.

My lymphoma is CD20 positive and is either stage II bulky or stage III/IV.

I have untreated FL with a FLIPI-1 score of 3-5, or I have relapsed/refractory FL without prior R-CHOP or R-CVP treatment.

Exclusion Criteria

My lymphoma has changed into a more aggressive form.

I have lymphoma in my brain or spinal cord.

I have been diagnosed with a specific type of blood cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1A: Dose Escalation

Non-randomized dose escalation of odronextamab with chemotherapy for safety and tolerability assessment

Up to 35 days

Part 1B: Dose Optimization

Randomized exploration of odronextamab regimens with chemotherapy for dose optimization

Up to 2 years

Part 2: Randomized Controlled

Comparison of odronextamab with chemotherapy versus rituximab with chemotherapy

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Cyclophosphamide (Anti-tumor antibiotic)
• Doxorubicin (Anti-tumor antibiotic)
• Odronextamab (Monoclonal Antibodies)
• Prednisone/Prednisolone (Corticosteroid)
• Rituximab (Monoclonal Antibodies)
• Vincristine (Vinca alkaloids)

Trial Overview The trial is testing odronextamab combined with chemotherapy against the standard rituximab with chemotherapy. It's divided into three parts: initial non-randomized phases to determine safe dosages and a final phase comparing effectiveness between treatments.

Participant Groups

Group I: Odronextamab + Chemotherapy + No maintenance Experimental Treatment 2 Interventions

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.

Group II: Odronextamab + Chemotherapy + Maintenance Experimental Treatment 2 Interventions

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy \[CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)\], followed by odronextamab monotherapy maintenance.

Group III: Odronextamab + Chemotherapy Experimental Treatment 4 Interventions

Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.

Group IV: Rituximab + Chemotherapy Active Control 6 Interventions

In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.

Cyclophosphamide is already approved in Canada, Japan for the following indications:

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

In a study of 675 patients aged 65 and older with follicular lymphoma, those who received the R-CHOP treatment as their first line of therapy had significantly longer overall survival compared to those who received it as a second line treatment.

The benefit of receiving R-CHOP as a first line was particularly notable in patients aged 80 and older and those with lower histological grades (1 or 2), indicating that early treatment may be crucial for improving outcomes in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. Xie, C., Li, R., Huang, X., et al.[2022]

In a long-term follow-up of 129 patients with advanced follicular lymphoma, the combination of rituximab with mitoxantrone, chlorambucil, and prednisolone (R-MCP) showed significantly improved overall survival compared to MCP alone, with 8-year survival rates of 76.1% versus 55.9%.

Patients receiving R-MCP also experienced longer progression-free survival (93.4 months) and event-free survival (89.6 months) compared to those on MCP alone, indicating that adding rituximab enhances long-term clinical outcomes for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. Herold, M., Scholz, CW., Rothmann, F., et al.[2018]

In a study of 22 patients with resistant and relapsed CD20-positive follicular non-Hodgkin's lymphoma, the combination treatment of rituximab, high-dose cytarabine, oxaliplatin, and dexamethasone (R-DHAOx) resulted in a remarkable 95% complete response rate, demonstrating its efficacy as a salvage therapy.

With a median follow-up of 58.3 months, the treatment showed long-term effectiveness, with an 84% progression-free survival rate at 38.2 months, although it was associated with significant side effects like peripheral neuropathy and myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma. Machover, D., Delmas-Marsalet, B., Misra, SC., et al.[2015]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Stem cell transplantation can significantly improve survival in patients with follicular lymphoma (FL), but many patients are ineligible due to age or other health issues, leading to reliance on salvage chemotherapy.

Salvage chemotherapy for relapsed FL often involves highly toxic agents that can cause severe side effects, including myelosuppression, nausea, and long-term risks like secondary cancers, highlighting the need for novel therapies to reduce these toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability. Zinzani, PL.[2006]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

The medication instruction sheet (MIS) developed for patients receiving R-CHOP therapy effectively predicted 71% of adverse drug reactions (ADRs) during the treatment period, demonstrating its usefulness in managing these reactions.

The MIS accurately matched the onset timing of infusion reactions and peripheral neuropathy, although its effectiveness was lower for predicting thrombocytopenia-related ADRs, indicating areas for improvement in monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. Uchida, M., Kawai, R., Hisamitsu, R., et al.[2022]

The combination of biweekly THP-COP chemotherapy and radiotherapy resulted in a high 5-year overall survival rate of 89% and a cause-specific survival rate of 90% in 41 patients with early-stage non-Hodgkin's lymphoma.

Despite some patients experiencing grade 4 neutropenia (12%), the treatment was well-tolerated, with 93% of patients completing the chemotherapy as scheduled, indicating that this regimen is both feasible and effective for low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Nishioka, T., Tsuchiya, K., Nishioka, S., et al.[2015]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

In a study of seven patients with non-Hodgkin lymphoma treated with rituximab (RTX) and chemotherapy, there was a significant reduction in their ability to mount an immune response to vaccines, indicating increased susceptibility to infections.

The introduction of intravenous immunoglobulin (IVIg) therapy was crucial for managing recurrent infections, such as pneumonia and sinusitis, highlighting the importance of monitoring and addressing hypogammaglobulinemia in patients undergoing RTX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. de Souza, KJ., Ferro, RS., Prestes-Carneiro, LE., et al.[2019]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

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]

2. Germany pubmed.ncbi.nlm.nih.gov

Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. [2018]

3. France pubmed.ncbi.nlm.nih.gov

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma. [2015]

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

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. [2016]

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

Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability. [2006]

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

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. [2022]

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

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. [2015]

9. Japan pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]

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

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. [2019]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]