Lenalidomide + Ibrutinib for Lymphoma

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

39 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drugs Lenalidomide and Ibrutinib for treating lymphoma?

Research shows that the combination of Lenalidomide and Ibrutinib is effective in treating certain types of lymphoma, such as mantle cell lymphoma and diffuse large B-cell lymphoma, with high response rates and manageable side effects. ^{1 2 3 4 5}

Is the combination of Lenalidomide and Ibrutinib safe for humans?

The combination of Lenalidomide and Ibrutinib has been studied in various trials for different types of lymphoma and multiple myeloma. Common side effects include anemia (low red blood cell count), neutropenia (low white blood cell count), and skin rashes, but these were generally manageable. Overall, the combination appears to be safe and well-tolerated in patients with relapsed or refractory conditions. ^{1 2 3 5 6}

How is the drug combination of Lenalidomide and Ibrutinib unique for treating lymphoma?

The combination of Lenalidomide and Ibrutinib is unique because it uses two drugs with different mechanisms to potentially enhance treatment effectiveness, especially in difficult-to-treat cases of lymphoma. This combination has shown promising results in improving response rates in patients with relapsed or refractory lymphoma, compared to using either drug alone. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib in treating patients with B-cell non-Hodgkin lymphoma that has returned (relapsed) or not responded to treatment (refractory). 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 cell growth. Giving lenalidomide with ibrutinib may work better in treating non-Hodgkin lymphoma than giving either drug alone.

Research Team

Beth A Christian

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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 do not have any uncontrolled illnesses or social situations that could affect my participation.

I am allergic to lenalidomide or similar drugs.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: A multicentre, non-randomised, open-label phase 2 study. [2023]

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

Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma. [2023]

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

Smart Start: Rituximab, Lenalidomide, and Ibrutinib in Patients With Newly Diagnosed Large B-Cell Lymphoma. [2023]

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

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: Phase I trial results. [2022]