Lenalidomide + Epcoritamab for Follicular Lymphoma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Aspirin, Blood thinners

Must not be taking: Live vaccines

Disqualifiers: CNS involvement, Active infection, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two treatments, lenalidomide and epcoritamab, work together to address untreated follicular lymphoma. Lenalidomide helps the immune system fight cancer cells by inhibiting their growth, while epcoritamab is a specialized antibody that targets and recruits immune cells to attack cancer cells. The trial aims to determine if combining these treatments is more effective than using them separately. Suitable participants have been diagnosed with follicular lymphoma requiring treatment and exhibit noticeable lymph node swelling. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must not be on certain treatments like anticoagulants unless specific conditions are met. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that using lenalidomide with epcoritamab may help treat follicular lymphoma. Studies have found that most patients tolerate this combination well. Common side effects of epcoritamab include injection site reactions, fatigue, and occasionally mild respiratory issues similar to a cold. Serious side effects are rare but can include cytokine release syndrome, where the immune system becomes overly active.

Lenalidomide is already approved for other uses, indicating its general safety. However, when combined with epcoritamab, monitoring for any new or increased side effects is important. Overall, despite some risks, the treatment remains safe enough for continued testing in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about lenalidomide and epcoritamab for follicular lymphoma because they bring a fresh approach to treating this condition. Epcoritamab is a bispecific antibody that targets CD3 on T-cells and CD20 on B-cells, which is different from many standard treatments that focus solely on one target. This dual targeting can potentially enhance the immune system's ability to attack cancer cells more effectively. Additionally, the combination with lenalidomide, an immunomodulatory drug, may boost the overall immune response against the lymphoma. This pairing offers a novel mechanism and delivery method that could lead to improved outcomes for patients.

What evidence suggests that lenalidomide and epcoritamab might be an effective treatment for follicular lymphoma?

Research has shown that both lenalidomide and epcoritamab are promising treatments for follicular lymphoma. Lenalidomide modulates the immune system to either boost or suppress itself, preventing cancer cell growth. Epcoritamab, a special antibody, enhances the immune system's ability to target and attack cancer cells. In this trial, participants will receive a combination of these two drugs, which studies have found to be more effective than using them separately. This combination has already demonstrated significant success in treating similar conditions, improving patient response to treatment and increasing survival rates. ^{1 6 7 8 9}

Who Is on the Research Team?

Swetha Kambhampati, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with untreated Follicular Lymphoma (FL) grade 1-3a who need treatment. They must have measurable lymphadenopathy or extranodal involvement, acceptable organ function tests, and for women of childbearing potential, a negative pregnancy test and agreement to use effective birth control. Excluded are those with certain heart conditions, active infections like hepatitis B/C or HIV, other recent malignancies, pregnant/breastfeeding women, and anyone unlikely to follow the study procedures.

Inclusion Criteria

My follicular lymphoma is confirmed and needs treatment according to GELF criteria.

My platelet count is at least 50,000 without bone marrow issues.

Your total bilirubin is no more than twice the maximum allowable concentration, except if you have Gilbert's disease.

Exclusion Criteria

I have HIV but it's under control with medication.

I am not pregnant, breastfeeding, nor plan to become pregnant soon.

My prostate cancer is being monitored or treated with hormones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide orally once daily on days 1-21 of each cycle and epcoritamab subcutaneously on days 1, 8, 15, and 21 of cycles 1-3 and on day 1 of each subsequent cycle. Treatment repeats every 28 days for up to 12 cycles.

12 months

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes safety checks on days 7, 30, and 60, active response monitoring every 6 months for up to 2 years, and survival monitoring every 6 months.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Lenalidomide

Trial Overview

The trial is testing the effectiveness of combining Lenalidomide (which affects the immune system and blood vessel growth in cancer cells) with Epcoritamab (a dual-action antibody that targets cancer cells more specifically). This phase II trial includes additional diagnostic procedures like bone marrow biopsy and imaging tests such as CT scans, MRIs, PET scans to monitor disease progression.

How Is the Trial Designed?

Group I: Treatment (lenalidomide and epcoritamab) Experimental Treatment 8 Interventions

Patients receive lenalidomide PO QD on days 1-21 of each cycle and epcoritamab SC on days 1, 8, 15, and 21 of cycles 1-3 and on day 1 of each subsequent cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may be re-treated with study treatment at any point during the follow-up period as long as they did not progress during treatment or stop due to unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI as well as bone marrow biopsy throughout the trial. Patients undergo blood sample collection on trial and during follow-up.

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

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Lenalidomide, an immunomodulatory drug, shows promise in treating diffuse large B-cell lymphoma (DLBCL) due to its multiple mechanisms of action that may enhance the effectiveness of existing immunochemotherapy treatments.

Current survival rates for DLBCL indicate a need for new treatment options, and lenalidomide has demonstrated potential benefits in both relapsed/refractory cases and as a first-line treatment based on recent clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in diffuse large B-cell lymphoma. Thieblemont, C., Delfau-Larue, MH., Coiffier, B.[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 significantly improves the complete response rate (CRR) in patients with diffuse large B-cell lymphoma (DLBCL), achieving a CRR of 47.7% compared to 37.8% in the control group, based on a meta-analysis of 6 randomized controlled trials involving 1938 patients.

While lenalidomide enhances progression-free survival (PFS), it is associated with a higher risk of severe hematological adverse events, particularly neutropenia and febrile neutropenia, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials. Liu, J., Mi, R., Chen, L., et al.[2023]

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]

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]

In a phase II trial involving 217 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, lenalidomide demonstrated an overall response rate of 35%, with 13% achieving complete remission and 22% achieving partial remission.

Lenalidomide was found to be well tolerated, although myelosuppression was a common side effect, particularly with grade 4 neutropenia occurring in 17% of patients, indicating that while effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Witzig, TE., Vose, JM., Zinzani, PL., et al.[2022]

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

In a phase II trial involving 66 patients with untreated follicular lymphoma, the combination of lenalidomide and rituximab achieved a high overall response rate of 95% and a complete response rate of 72%, indicating strong efficacy.

The treatment was associated with low rates of severe toxicity (grade 3-4), with a 5-year overall survival rate of 100%, suggesting that lenalidomide plus rituximab could be a safe and effective alternative to traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Martin, P., Jung, SH., Pitcher, B., et al.[2023]

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