Lenalidomide + Blinatumomab for Lymphoma

No longer recruiting at 25 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Efavirenz, Stavudine, Zidovudine

Disqualifiers: Brain metastases, Uncontrolled illness, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs, lenalidomide and blinatumomab, to determine the optimal dose and monitor side effects in individuals with recurrent non-Hodgkin lymphoma. Lenalidomide can modulate the immune system to inhibit cancer growth, while blinatumomab (also known as Blincyto) aims to prevent cancer cells from spreading. The trial targets those whose non-Hodgkin lymphoma has returned after at least two different treatments. Participants should have a type of lymphoma that tests positive for the CD19 marker. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other anti-cancer treatments or certain HIV medications with similar side effects. Any prior therapy must have been completed at least 4 weeks before joining the study.

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

Research has shown that both blinatumomab and lenalidomide have been tested for safety in treating non-Hodgkin's lymphoma that has returned after treatment. Studies found that blinatumomab can lead to long-term remission, meaning the cancer stays away longer. These studies suggest that a dose of 60 µg/m² per day is generally safe for patients. Lenalidomide, a type of biological therapy, effectively stops cancer cells from growing.

When combined, researchers focus on finding the best dose and checking for any side effects. This combination is used in patients whose non-Hodgkin's lymphoma has returned or didn't respond to previous treatments. The research mainly aims to understand how the body handles these drugs together and what side effects might occur.

In trials like this, the main goal is to ensure the treatment is safe for people. So far, the information suggests that while side effects exist, careful monitoring can manage them. This trial is in an early phase, meaning researchers are still learning the best way to use these drugs together and ensuring they are safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of lenalidomide and blinatumomab for treating lymphoma because it introduces a novel approach to targeting cancer cells. Lenalidomide is an immunomodulatory drug that enhances the immune system's ability to fight cancer, while blinatumomab is a bispecific T-cell engager (BiTE) antibody that brings T-cells directly to cancer cells, prompting a targeted immune attack. Unlike standard treatments that might rely on chemotherapy alone, this combination harnesses the power of the immune system, potentially offering a more precise and effective way to combat lymphoma. This dual-action method could lead to improved outcomes with potentially fewer side effects, sparking hope for more efficient lymphoma management.

What evidence suggests that lenalidomide and blinatumomab might be effective for non-Hodgkin lymphoma?

Studies have shown that both blinatumomab and lenalidomide can help treat relapsed or refractory non-Hodgkin's lymphoma (NHL). Blinatumomab may lead to long-term remission and extend patient survival, while lenalidomide aids the immune system in halting cancer cell growth. This trial will administer a combination of these two drugs to determine if their combined use enhances effectiveness against the cancer. Although both treatments show promise, they have certain limitations. ^{1 2 3 4 5}

Who Is on the Research Team?

Joseph M. Tuscano

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with various types of relapsed Non-Hodgkin Lymphoma who have tried at least two prior treatments and are not eligible for standard cures. They must have measurable disease, normal organ function tests, no brain metastases or uncontrolled illnesses, and not be pregnant or breastfeeding. HIV-positive patients can join if they meet certain conditions.

Inclusion Criteria

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal

Patients must have radiographically measurable disease

Platelets >= 50,000/mcL

Exclusion Criteria

Patients receiving any other investigational agents

I have an active hepatitis B or C infection.

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49

8 weeks

Consolidation

Patients achieving response receive blinatumomab IV on days 1-7 and lenalidomide PO on days 1-21, repeating every 28 days for up to 6 cycles

24 weeks

Maintenance

Patients receive lenalidomide PO on days 1-21, repeating every 28 days for up to 2 years

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Lenalidomide

Trial Overview The trial is testing the combination of Lenalidomide and Blinatumomab to find the safest doses and observe side effects in treating relapsed Non-Hodgkin Lymphoma. Lenalidomide boosts the immune system while Blinatumomab targets cancer cells directly.

How Is the Trial Designed?

Group I: Treatment (blinatumomab, lenalidomide) Experimental Treatment 2 Interventions

INDUCTION: Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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]

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 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]

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, an immunomodulatory drug used to treat multiple myeloma, has been associated with an increased risk of developing secondary primary malignancies, including high-grade astrocytomas like glioblastoma multiforme, as evidenced by a case study of a 72-year-old man.

This case marks the first reported instance of glioblastoma multiforme occurring after lenalidomide treatment in a patient with multiple myeloma, highlighting the need for awareness of this potential risk among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review. Moore, CA., Ibrahim, M., Kapila, A., et al.[2019]

Lenalidomide is an effective oral immunomodulator approved for treating relapsed/refractory mantle cell lymphoma (MCL) after two prior therapies, showing significant activity in various B-cell non-Hodgkin lymphomas (NHL).

Combining lenalidomide with rituximab (R2) has demonstrated promising results in both first-line and relapsed/refractory settings, and ongoing trials are evaluating its use in combination with immunochemotherapy regimens like R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Witzig, TE., Nowakowski, GS., Habermann, TM., et al.[2020]

Lenalidomide is an effective oral treatment for various hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), with different starting doses based on the type of cancer.

Common side effects like neutropenia and thrombocytopenia can be managed effectively with proper monitoring and prophylaxis, allowing for safer administration and improved patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. Blumel, S., Broadway-Duren, J.[2020]

Citations

1. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/760/426926/Blinatumomab-Lenalidomide-in-Relapsed-Refractory

Blinatumomab/Lenalidomide in Relapsed/Refractory Non ... Both blinatumomab and lenalidomide have proven, but limited, efficacy in relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02568553

NCT02568553 | Lenalidomide and Blinatumomab for the ... This phase I trial studies the side effects and best dose of lenalidomide and blinatumomab when given together in treating patients with non-Hodgkin ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6712531/

Long-term outcome of patients with relapsed/refractory B-cell ... Blinatumomab treatment leads to long-term remission and improved median OS for patients with R/R B-NHL. A dose of 60 µg/m2 per day seems to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118586778

Blinatumomab/Lenalidomide in Relapsed/Refractory Non- ... Both blinatumomab and lenalidomide have proven, but limited, efficacy in relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). Failure of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02568553?term=AREA%5BBasicSearch%5D(medi%20538)&rank=2

Study Details | Lenalidomide and Blinatumomab for the ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...