Lenalidomide + Ibrutinib for Lymphoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, Anticoagulants

Disqualifiers: Active CNS involvement, Cardiovascular disease, Hepatic impairment, 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

Duration: 28 days per cycle, repeated

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining lenalidomide (Revlimid) and ibrutinib (Imbruvica) for treating B-cell non-Hodgkin lymphoma that has recurred or resisted previous treatments. Lenalidomide may shrink the cancer, while ibrutinib could inhibit cancer cell growth by blocking essential enzymes. The trial aims to determine the optimal dosage and understand the side effects of using these drugs together. It is suitable for individuals diagnosed with specific types of B-cell non-Hodgkin lymphoma who have undergone at least one prior treatment but still experience symptoms. 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 combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take medications that strongly affect certain liver enzymes (CYP3A4) or those that cause heart rhythm issues. You also cannot be on blood thinners like warfarin or strong immunosuppressants.

Is there any evidence suggesting that lenalidomide and ibrutinib are likely to be safe for humans?

Research has shown that the combination of lenalidomide and ibrutinib has been tested in other studies. These studies found that this combination is generally well-tolerated, though some patients experienced more serious side effects, such as rashes. Despite these side effects, the treatment effectively fought certain types of cancer.

Both lenalidomide and ibrutinib have been used individually and are already approved for other conditions, indicating that their safety is well-understood and monitored. However, the combination is still under study to ensure its safety and effectiveness for treating non-Hodgkin lymphoma. Prospective participants should consider these points when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using lenalidomide and ibrutinib for lymphoma because this combination targets cancer cells in a novel way. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, ibrutinib specifically inhibits a protein involved in the survival and spread of lymphoma cells, while lenalidomide boosts the immune system to fight cancer. This dual approach could potentially offer more effective disease control with fewer side effects. By attacking lymphoma from two different angles, this combination holds the promise of improved outcomes over existing treatments.

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

Research has shown that lenalidomide can reduce or slow the growth of non-Hodgkin lymphoma. Ibrutinib may block certain proteins that cancer cells need, preventing their growth. In this trial, participants will receive a combination of lenalidomide and ibrutinib. A similar combination with rituximab has demonstrated promising results in other studies, with an overall response rate of 86% in some patients. This suggests that using lenalidomide and ibrutinib together could effectively treat non-Hodgkin lymphoma, especially when other treatments have failed. The treatment also has a manageable safety profile, with generally tolerable side effects. ^{2 3 6 7 8}

Who Is on the Research Team?

Beth A Christian

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of B-cell non-Hodgkin lymphoma that have relapsed or are refractory. Participants must have had at least one prior therapy, be in fairly good health (ECOG <=2), and not pregnant or nursing. They should understand the study and consent to participate. Those with active infections, recent major surgery, known allergies to trial drugs, or on specific medications are excluded.

Inclusion Criteria

Non-pregnant and non-nursing

All possible curative treatments have been tried or are not suitable for me.

I have had at least one treatment before, including a stem cell transplant.

Exclusion Criteria

I need medication to prevent blood clots.

I am allergic to lenalidomide or similar drugs.

I haven't had any infections needing treatment recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide orally on days 1-21 and ibrutinib orally on days 1-28 in 28-day cycles

28 days per cycle, repeated

Regular visits for blood sample collection and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks initially, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Lenalidomide

Trial Overview The trial is testing the combination of two drugs: Lenalidomide and Ibrutinib. It aims to find the safest dose while assessing how well these drugs work together against various subtypes of B-cell non-Hodgkin lymphoma compared to using them separately.

How Is the Trial Designed?

Group I: Treatment (lenalidomide, ibrutinib) Experimental Treatment 8 Interventions

Patients receive lenalidomide PO on days 1-21 and ibrutinib PO on days 1-28 (days 2-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT or PET/CT throughout the study. Patients may undergo bone marrow biopsy and aspiration and MRI as clinically indicated.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

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

In a phase 2 trial involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib, lenalidomide, and rituximab resulted in a high overall response rate of 76%, with 56% achieving a complete response, suggesting this triplet therapy is effective.

While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment-related deaths, highlighting the need for careful monitoring and further evaluation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Jerkeman, M., Eskelund, CW., Hutchings, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6764267/

Ibrutinib plus lenalidomide and rituximab has promising ... In conclusion, the triplet of ibrutinib, lenalidomide, and rituximab demonstrated promising activity and a manageable safety profile in patients with relapsed/ ...

2. onclive.com onclive.com/view/ibrutinib-lenalidomide-rituximab-yields-long-term-efficacy-in-r-r-mcl

Ibrutinib/Lenalidomide/Rituximab Yields Long-Term ... Primary findings showed that ibrutinib plus lenalidomide and rituximab generated an ORR of 86% (95% CI, 73.3%-93.6%) and was active in patients ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6260/505326/Real-World-Efficacy-and-Safety-of-Rituximab

Real-World Efficacy and Safety of Rituximab, Lenalidomide ... Our results suggest that RLI is a viable therapeutic option with promising activity and favorable toxicity profile in patients with R/R NHL patients.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01955499

Study Details | NCT01955499 | Lenalidomide and Ibrutinib ... Lenalidomide helps shrink or slow the growth of non-Hodgkin lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00508-9/fulltext

The iR2 regimen (ibrutinib plus lenalidomide and rituximab ... In conclusion, the combination of ibrutinib, lenalidomide, and rituximab demonstrated encouraging antitumour activity with durable responses and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37985359/

Safety and efficacy of ibrutinib in combination with rituximab ... Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 toxicity, particularly rash. The study was ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02077166

Study Details | NCT02077166 | Ibrutinib in Combination ... This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/ ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35114

Safety and efficacy of ibrutinib in combination with rituximab ... In patients treated with lenalidomide and rituximab in the RELEVANCE trial, the ORR was 61% and CRR was 48%. CRR at 120 weeks was 48%. The 6- ...