Ibrutinib + Lenalidomide + Rituximab for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hackensack Meridian Health

Must be taking: Aspirin

Must not be taking: Warfarin

Disqualifiers: CNS involvement, HIV, Hepatitis, 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: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three treatments—ibrutinib (Imbruvica), lenalidomide (Revlimid), and rituximab (Rituxan, Riabni, Ruxience, or Truxima)—for individuals with mantle cell lymphoma, a cancer affecting lymph nodes that has returned or not responded to previous treatments. The main goal is to determine the safest and most effective doses of these drugs when used together. Individuals diagnosed with mantle cell lymphoma, who have undergone at least one treatment, and have a measurable lymph node or mass, might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

The trial does not specify if you need to stop taking your current medications, but you cannot use warfarin or other Vitamin K antagonists. Also, you must not have used any standard chemotherapy, radiation therapy, or experimental drug therapy for MCL within 21 days before starting the trial.

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

Research has shown that the combination of ibrutinib, lenalidomide, and rituximab is generally safe, though it can cause serious side effects. Studies have found a higher likelihood of severe side effects, such as significant rashes. However, another study suggested that this treatment could be effective and safe for patients with relapsed or hard-to-treat non-Hodgkin lymphoma.

While these findings are promising, it's important to note that this trial is in its early stages. The main goal is to determine the best dose and monitor any side effects. Prospective participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ibrutinib, Lenalidomide, and Rituximab for lymphoma because each of these drugs targets the disease in a unique way. Ibrutinib stands out by inhibiting Bruton's tyrosine kinase, which is crucial for the survival of cancer cells. Lenalidomide modulates the immune system to enhance its ability to fight cancer, while Rituximab targets and destroys specific cancer cells by binding to a protein called CD20 on their surface. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, this combination offers a more targeted approach, potentially leading to fewer side effects and improved efficacy.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

Research has shown that the combination of ibrutinib, lenalidomide, and rituximab is promising for treating mantle cell lymphoma that has returned or is unresponsive to treatment. In this trial, participants will receive this combination, known as the iR2 regimen. Specifically, this treatment has extended the time patients live without cancer worsening, with an average of 17.4 months before progression and an overall survival time of 45.3 months. Studies indicate that this combination is effective and generally safe for patients with similar types of lymphoma. It is considered a good option for those with challenging cases of lymphoma. ^{1 3 4 5 6}

Who Is on the Research Team?

Andre Goy, MD

Principal Investigator

Hackensack Meridian Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Mantle Cell Lymphoma that has come back or hasn't responded to treatment. They must have had at least one prior therapy, be in decent physical shape (ECOG ≤2), and have certain blood counts within normal ranges. Women who can have children need a negative pregnancy test and must follow specific safety programs.

Inclusion Criteria

My diagnosis of mantle cell lymphoma (MCL) is confirmed by lab tests.

I have at least one measurable tumor or lymph node.

My kidney function is normal, with a creatinine level below 2.

Exclusion Criteria

Other medical conditions that would potentially interfere with patient participation in this trial

I am currently taking warfarin or similar blood thinners.

I do not have a serious infection or it has been treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Treatment

Participants receive ibrutinib, lenalidomide, and rituximab to determine the maximum tolerated dose (MTD) and/or recommended phase II dose

6 cycles

Response is evaluated after 2, 4, and 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Through 28 days after discontinuation of study drug

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Lenalidomide
• Rituximab

Trial Overview The study aims to find the safest dose of Ibrutinib combined with Lenalidomide/Rituximab for patients with relapsed/refractory Mantle Cell Lymphoma. It's a step-by-step process where doses are increased to determine the maximum tolerated dose or recommended phase II dose.

How Is the Trial Designed?

Group I: Dose Escalation Study Experimental Treatment 3 Interventions

Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 10-25 mg PO days 1-21

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?

Hackensack Meridian Health

Lead Sponsor

Trials

141

Recruited

42,900+

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]

The combination of rituximab and ibrutinib in a 57-year-old patient with mantle cell lymphoma led to a severe disseminated enterovirus infection, highlighting the significant risk of immunodeficiency and severe immune-related side effects from this treatment regimen.

High-dose intravenous immunoglobulins were effective in clearing the virus and restoring organ function, suggesting that this treatment should be considered for patients experiencing severe enterovirus infections while on rituximab and ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report. Higer, M., Cana, D., Podlech, J., et al.[2021]

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]

Ibrutinib, a Bruton's kinase inhibitor, has shown a high overall response rate of 68% in patients with relapsed or refractory mantle cell lymphoma, with a median progression-free survival of 13.9 months, indicating its efficacy as a treatment option.

In a phase 3 trial for chronic lymphocytic leukemia, ibrutinib demonstrated a significantly higher response rate (43% vs. 4% for ofatumumab) and improved overall survival (90% vs. 81% at 12 months), while being well tolerated with no dose-limiting toxicity, making it a suitable option for older patients and those not eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib. Lee, CS., Rattu, MA., Kim, SS.[2021]

Citations

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

Safety and efficacy of ibrutinib in combination with rituximab ... IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 ...

2. 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.

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

Ibrutinib/Lenalidomide/Rituximab Yields Long-Term ... The IR2 regimen showed durable responses in relapsed/refractory MCL, with a median PFS of 17.4 months and OS of 45.3 months. · Superior survival ...

4. 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/ ...

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

The iR2 regimen (ibrutinib plus lenalidomide and rituximab ... This phase 1b/2 PCYC-1123-CA study evaluated efficacy and safety of the combination of ibrutinib, lenalidomide, and rituximab (iR2 regimen) in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10922670/

Safety and Efficacy of Ibrutinib in Combination with Rituximab ... Here we report the results of a frontline, open-label, phase II clinical trial of ibrutinib, lenalidomide and rituximab for previously untreated patients with ...