What side effects are associated with this type of intervention?

The combination of Lenalidomide and Rituximab for treating Follicular Lymphoma can lead to several side effects. Lenalidomide is known to increase the risk of serious infections, cause hematologic toxicities like neutropenia and thrombocytopenia, and result in non-hematologic issues such as fatigue and gastrointestinal problems. Rituximab often causes infusion-related reactions, particularly during the first treatment cycle, which can include fever, chills, and hypotension. Patients receiving this combination therapy may experience a mix of these side effects, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Follicular Lymphoma that involve immunomodulation and CD20-targeted B-cell destruction. Rituximab, a monoclonal antibody targeting CD20, has been a cornerstone in the treatment of Follicular Lymphoma, often used in combination with chemotherapy regimens such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) or Bendamustine. Lenalidomide, an immunomodulatory drug, has also been studied in combination with Rituximab (R2 regimen) and has shown efficacy in treating Follicular Lymphoma. These combinations aim to enhance the immune response against lymphoma cells while directly targeting and destroying B-cells.

What other types of research exist?

Promising novel alternatives for Follicular Lymphoma patients include: 1) CAR T-cell therapies such as axicabtagene ciloleucel and tisagenlecleucel, which have shown significant efficacy in relapsed/refractory cases. 2) Bispecific antibodies like mosunetuzumab, which target both CD20 and CD3, engaging T-cells to kill B-cells. 3) Next-generation BTK inhibitors such as zanubrutinib and acalabrutinib, which offer improved safety and efficacy profiles. 4) PI3K inhibitors like umbralisib, which target signaling pathways crucial for B-cell survival. These alternatives provide diverse mechanisms of action and have demonstrated promising results in clinical settings.

← Back to Search

Immunomodulatory Agent

Rituximab + Lenalidomide for Follicular Lymphoma (RELEVANCE Trial)

Phase 3

Waitlist Available

Research Sponsored by Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed follicular lymphoma grade 1, 2 or 3a, Stage II-IV

Symptomatic follicular lymphoma requiring treatment

Must not have

Presence or history of central nervous system involvement by lymphoma

At high risk for a venous thromboembolic event (VTE) and not willing to take VTE prophylaxis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 2.5 years

Awards & highlights

Approved for 10 Other Conditions

All Individual Drugs Already Approved

Pivotal Trial

No Placebo-Only Group

Summary

This trial uses lenalidomide and rituximab to treat patients with Follicular Lymphoma. The treatment aims to fix immune system issues and help the body fight the cancer more effectively. Lenalidomide is a drug approved in the United States for use with rituximab in patients with this type of lymphoma.

Who is the study for?

This trial is for adults with symptomatic follicular lymphoma grades 1, 2, or 3a at stages II-IV who haven't had systemic treatment. Participants should be able to perform daily activities (ECOG status 0-2) and agree to pregnancy precautions. Excluded are those allergic to murine products, with CNS lymphoma involvement, high VTE risk unwilling to take prophylaxis, certain lab abnormalities, transformed/Grade 3b lymphoma, recent major surgery or active hepatitis B/C or HIV.

What is being tested?

The study tests the effectiveness of combining lenalidomide and rituximab in treating Follicular Lymphoma compared to standard chemo combinations like Rituximab-CVP/CHOP/Bendamustine. It aims to control the disease better and extend the period patients remain responsive without signs of progression.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as infusion reactions from rituximab; blood cell count changes; fatigue; digestive issues from lenalidomide; increased risk of infections and possibly deep vein thrombosis due to heightened clotting tendency.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My lymphoma is confirmed to be of a specific type and stage.

Select...

I have symptoms from follicular lymphoma that need treatment.

Select...

I am 18 years old or older.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

I have not received any systemic treatment for lymphoma.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My lymphoma has affected or previously affected my brain or spinal cord.

Select...

I am at high risk for blood clots and choose not to take preventive medication.

Select...

My lymphoma has changed in its nature or is a high-grade type.

Select...

I have not had major surgery in the last 28 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression free survival (PFS)Follicular lymphoma

Secondary study objectives

Complete Response Rate (CR/CRu) at 120 weeks

Event-Free Survival (EFS)

Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients

+5 more

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Lenalidomide + RituximabExperimental Treatment2 Interventions

* Lenalidomide dose 20-mg on days 2-22 every 28 days for 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3\~6 cycles and then 10 mg on days 2-22 every 28-day cycles for up to 18 cycles. * Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Group II: ControlActive Control3 Interventions

• ONE of the following: Rituximab-CHOP, Rituximab-CVP, Rituximab-Bendamustine. 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Rituximab

FDA approved

Lenalidomide

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lenalidomide and rituximab are common treatments for Follicular Lymphoma. Lenalidomide works by enhancing the immune system's ability to attack cancer cells, promoting T-cell and NK cell activity, and inhibiting angiogenesis and cytokine release. Rituximab targets the CD20 antigen on B-cells, leading to their destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These mechanisms are crucial for Follicular Lymphoma patients as they provide a targeted approach to eliminate malignant B-cells while modulating the immune response to sustain long-term remission.

Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma.