Lenalidomide + Rituximab for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, 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 cycles (approximately 12 months)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining lenalidomide and rituximab can effectively control chronic lymphocytic leukemia (CLL) and if their combined use is safe. Lenalidomide (Revlimid) may enhance the immune system and slow tumor growth, while rituximab targets and destroys cancer cells. Suitable participants have CLL that is either untreated or has recurred after previous treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

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

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

Research shows that using lenalidomide and rituximab together may help treat Chronic Lymphocytic Leukemia (CLL). Studies have found that many people tolerate this treatment well, though side effects can occur, as with any medication. Some patients experienced mild side effects, while others had more serious ones.

Lenalidomide boosts the immune system and slows cancer cell growth. It is already approved for other uses, providing extensive safety information. Rituximab targets and kills cancer cells and is also a well-known treatment. Trials have demonstrated that these two drugs work well for many patients. Most side effects can be managed, but discussing potential risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Lenalidomide and Rituximab for treating Chronic Lymphocytic Leukemia (CLL) because this duo offers a unique approach compared to traditional treatments like chemotherapy or single-agent therapies. Lenalidomide works by enhancing the immune system's ability to fight cancer cells, while Rituximab directly targets and eliminates specific cancer cells. This combination has the potential to provide a more effective treatment by attacking the cancer from multiple angles, potentially leading to better outcomes and longer-lasting responses. Additionally, this regimen might offer an option for patients who are older or have relapsed after previous treatments, addressing unmet needs in CLL care.

What evidence suggests that the combination of lenalidomide and rituximab could be effective for chronic lymphocytic leukemia?

Research shows that combining lenalidomide and rituximab effectively treats chronic lymphocytic leukemia (CLL). In this trial, participants will receive this combination, with one arm for patients of any age with previously treated CLL/SLL and recurrent disease, and another arm for untreated patients aged 65 or older with indications for treatment. Studies have found that many patients experience a reduction in cancer cells with this treatment. Ten-year follow-up data suggest that it can control CLL for a long time without major safety concerns. Previous research also found that patients with certain traits, like low levels of a protein called β2-microglobulin, responded particularly well. Overall, this combination of drugs has shown promise for both newly diagnosed and previously treated patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Alessandra Ferrajoli, MD,BS

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), either untreated and needing treatment but not suitable for chemoimmunotherapy, or those previously treated. Participants must have proper kidney and liver function, be in a stable health condition, not pregnant, willing to follow birth control requirements if applicable, and free from other serious illnesses.

Inclusion Criteria

All study participants must be registered into the mandatory RevAssist program and be willing and able to comply with the program requirements

I can take care of myself and perform daily activities.

My kidney function is good, with creatinine at or below 2mg/dL.

Exclusion Criteria

I am allergic to lenalidomide, thalidomide derivatives, or rituximab.

My blood test shows over 55% prolymphocytes, indicating prolymphocytic leukemia.

I do not have any serious health issues that would make joining this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide and rituximab in 28-day cycles. Rituximab is administered weekly during Cycle 1, not given in Cycle 2, and then on Day 1 of Cycles 3-12. Lenalidomide is taken daily starting Day 9 of Cycle 1.

12 cycles (approximately 12 months)

Weekly visits during Cycle 1, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Bone marrow biopsy and aspiration are performed at the end of Cycles 3, 6, and 12.

6 months

Visits at the end of Cycles 3, 6, and 12

Extension

Participants may continue treatment beyond 12 cycles if there is a significant benefit such as an ongoing Partial Response or Complete Response.

Indefinite, based on response

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Rituximab

Trial Overview The study tests the effectiveness of combining two drugs: Lenalidomide which boosts the immune system and may block blood vessels that support tumor growth; and Rituximab which targets cancer cells to destroy them. The safety of this combination therapy for CLL/SLL is also being evaluated.

How Is the Trial Designed?

Group I: Untreated 65 + Experimental Treatment 2 Interventions

Patients with untreated SLL/CLL with indications for treatment that are age 65 or older. Rituximab (375 mg/m2) will be given intravenously on Day 1, Day 8, Day 15 and Day 22 and then continued once every 4 weeks during cycles 3-12 (+ 7 days). Rituximab will not be given in Cycle 2. Lenalidomide will be started on Day 9 of cycle 1 at the dose of 10 mg/day and will be continued daily. Treatment duration will be 12 cycles and it will be possible to continue beyond 12 cycles if there is a significant benefit such as an ongoing Partial Response or Complete Response.

Group II: Prior Treatment Any Age Experimental Treatment 2 Interventions

Patients of any age with previously treated CLL/SLL and recurrent disease. Rituximab (375 mg/m2) will be given intravenously on Day 1, Day 8, Day 15 and Day 22 and then continued once every 4 weeks during cycles 3-12 (+ 7 days). Rituximab will not be given in Cycle 2. Lenalidomide will be started on Day 9 of cycle 1 at the dose of 10 mg/day and will be continued daily. Treatment duration will be 12 cycles and it will be possible to continue beyond 12 cycles if there is a significant benefit such as an ongoing Partial Response or Complete Response.

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01446133

Combination of Lenalidomide and Rituximab in Chronic ... The goal of this clinical research study is to learn if the combination of lenalidomide and rituximab can help to control CLL. The safety of this drug ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4878047/

Phase II Study of Lenalidomide and Rituximab As Salvage ... We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL.

3. cllsociety.org cllsociety.org/2024/07/long-term-outcoes-after-lenalidomide-plus-rituximab-for-cll/

Long-term Outcomes After Lenalidomide plus Rituximab for ... Ten-year follow-up data showed that lenalidomide plus rituximab produced high response rates in patients with CLL with no significant safety signals.

4. ashpublications.org ashpublications.org/bloodadvances/article/3/9/1533/246786/Efficacy-and-predictors-of-response-of

Efficacy and predictors of response of lenalidomide and ... The combination of lenalidomide and rituximab is highly effective in patients with CLL and low baseline β2-microglobulin levels.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.00843

Six-Year Results From RELEVANCE: Lenalidomide Plus ... The combination of lenalidomide and rituximab (ie, R2) has shown promising activity with high response rates in patients with previously ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00759603

Lenalidomide and Rituximab as Treatment of Chronic ... The goal of this clinical research study is to learn if the combination of lenalidomide and rituximab can help to control Chronic Lymphocytic Leukemia (CLL) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4067945/

Lenalidomide and Rituximab for the Initial Treatment ... Lenalidomide and rituximab represents a highly active immune-based therapy approach for treatment-naive CLL patients, in particular those with high-risk ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2152265020301427

Management of Adverse Events From the Combination ... Recent results from the phase 3 Augment trial showed that combining rituximab with the immunomodulatory drug lenalidomide (R2) significantly improved efficacy ...