Rituximab + Pembrolizumab +/- Lenalidomide for Lymphoma

Overseen By Clinical Research Operations UT MD Anderson Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Rituximab, CAR T cell

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active CNS lymphoma, 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: 3

Duration: 1-2 years

53 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Rituximab, Pembrolizumab, and Lenalidomide for lymphoma?

Research shows that Lenalidomide combined with Rituximab is effective for treating certain types of lymphoma, especially in patients who have not responded to Rituximab alone. This combination has been shown to improve outcomes in patients with follicular lymphoma and other B-cell lymphomas. ^{1 2 3 4 5}

Is the combination of Rituximab, Pembrolizumab, and Lenalidomide safe for treating lymphoma?

The combination of Rituximab and Lenalidomide has been studied for lymphoma and is generally considered safe, with common side effects including low white blood cell counts, skin rashes, and digestive issues, which are usually manageable. Pembrolizumab, another drug in this combination, is also used in cancer treatments and has a known safety profile, but specific safety data for the three drugs combined is not detailed in the provided research. ^{1 4 6 7 8}

What makes the drug combination of Rituximab, Pembrolizumab, and Lenalidomide unique for treating lymphoma?

This drug combination is unique because it combines the immunomodulatory effects of Lenalidomide, which enhances the immune system's ability to fight cancer, with Rituximab, an antibody that targets cancer cells, and Pembrolizumab, which helps the immune system recognize and attack cancer cells. This combination may offer a chemotherapy-free option that could be more effective for patients who have not responded to other treatments. ^{1 2 3 4 9}

What is the purpose of this trial?

This phase II trial studies how well rituximab and pembrolizumab with or without lenalidomide works in treating patients with follicular lymphoma and diffuse large B-cell lymphoma that has returned after a period of improvement. Immunotherapy with monoclonal antibodies, such as rituximab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rutuximab with pembrolizumab and lenalidomide may work better at treating follicular lymphoma and diffuse large B-cell lymphoma.

Research Team

Ranjit Nair

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with relapsed follicular lymphoma or diffuse large B-cell lymphoma after at least one prior therapy including rituximab, or two therapies with CAR T cell treatment. Participants must have adequate organ function, not be pregnant or breastfeeding, agree to use contraception, and cannot have certain infections like HIV or hepatitis.

Inclusion Criteria

Creatinine clearance will be calculated per institutional standard

Either the subject or his/her legally authorized representative be willing and able to provide written informed consent for the trial

Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

I have fully recovered from any major surgery before starting treatment.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have been treated with specific immune system targeting drugs before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive rituximab and pembrolizumab, with or without lenalidomide, depending on the cohort. Treatment cycles last up to 1 year for Cohort I and up to 2 years for Cohort II.

1-2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days, every 3 months for 1 year, and then every 6 months thereafter.

Up to 2 years

Regular follow-up visits

Treatment Details

Interventions

• Lenalidomide
• Pembrolizumab
• Rituximab

Trial Overview The study tests the effectiveness of combining rituximab and pembrolizumab with or without lenalidomide in treating patients whose lymphoma has returned. It examines how these drugs might help the immune system fight cancer and stop tumor growth.

Participant Groups

Group I: Cohort II (rituximab, pembrolizumab, lenalidomide) Experimental Treatment 4 Interventions

Patients receive rituximab IV over 4-8 hours on days 1, 8 and 15 of cycle 1, and day 1 of cycle 2. Patients also receive pembrolizumab IV over 1 hour on day 2 every 3 weeks for up to 2 years, and lenalidomide PO on days 1-14 every 3 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Cohort I (rituximab, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive rituximab IV over 4-8 hours on days 1, 8, 15, and 22. Patients also receive pembrolizumab IV over 1 hour on day 2 every 3 weeks for up to 16 cycles (1 year) in the absence of disease progression or unacceptable toxicity.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 50 patients with indolent B-cell or mantle cell lymphomas who were previously resistant to rituximab, the combination of lenalidomide and rituximab resulted in a significant increase in overall response rate from 30.2% after lenalidomide alone to 62.8% after adding rituximab.

The median progression-free survival for patients receiving the lenalidomide-rituximab combination was 22.2 months, which was significantly longer than the 9.13 months observed with prior rituximab treatment, indicating that this combination can effectively overcome previous resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Chong, EA., Ahmadi, T., Aqui, NA., et al.[2022]

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 a phase 2 trial involving 27 patients with rituximab-resistant B-cell lymphomas, the combination of lenalidomide, low-dose dexamethasone, and rituximab resulted in a significant increase in overall response rates from 29% after initial treatment to 58% after adding rituximab.

The median progression-free survival for patients was 23.7 months, indicating that this combination therapy not only enhances response rates but also provides durable benefits for patients with difficult-to-treat lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Ahmadi, T., Chong, EA., Gordon, A., et al.[2018]

In a phase II study involving 59 adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL), the combination of lenalidomide and rituximab resulted in a 66% overall response rate, indicating significant efficacy as a salvage therapy.

While the treatment showed promise, it was associated with notable side effects, particularly neutropenia in 73% of patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. Badoux, XC., Keating, MJ., Wen, S., et al.[2021]

The combination of rituximab and lenalidomide (R2) significantly improves treatment efficacy for recurrent non-Hodgkin lymphoma compared to rituximab alone, leading to its approval for use in previously treated patients with follicular and marginal zone lymphoma.

R2 has a manageable safety profile, with common adverse events including grade 3/4 neutropenia, skin rashes, and gastrointestinal issues, indicating that while it is effective, careful monitoring and management of side effects are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. Cheson, BD., Morschhauser, F., Martin, P.[2021]

Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

Lenalidomide is an effective and well-tolerated treatment for multiple myeloma and shows promise for patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma.

The review highlights the potential of lenalidomide, especially in combination with rituximab, as a therapeutic option, aiming to guide future clinical studies to enhance survival rates for these lymphoma types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy. Desai, M., Newberry, KJ., Romaguera, J., et al.[2021]

References

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

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]

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

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]

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

Lenalidomide in follicular lymphoma. [2021]

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

Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. [2018]

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

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. [2021]

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

Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]

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

Real-World, Single-Center Data for Lenalidomide Plus Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy. [2021]