Ibrutinib for Chronic Lymphocytic Leukemia

(MERIT Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Warfarin, Strong CYP3A modulators

Disqualifiers: Pregnancy, Active hepatitis, HIV, 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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 144-148 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of ibrutinib for people with chronic lymphocytic leukemia (CLL) who have residual disease after initial treatment. Ibrutinib works by blocking certain enzymes that cancer cells need to grow. The study seeks participants who have undergone CLL treatment but still have remaining cancer cells. It suits those who have completed initial therapy and are not currently experiencing disease progression. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use warfarin, other vitamin K antagonists, or strong cytochrome P450 modulators while participating in the trial.

Is there any evidence suggesting that ibrutinib is likely to be safe for humans?

Research has shown that ibrutinib is generally well-tolerated by people with chronic lymphocytic leukemia (CLL). In a real-world study, patients responded well to the treatment, finding it effective even for those with higher risk factors. Another study confirmed that ibrutinib was safe for long-term use, with no new safety concerns arising. While some patients experienced side effects, these did not worsen over time. Overall, ibrutinib maintains a strong safety record for treating CLL. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for chronic lymphocytic leukemia (CLL) involve chemotherapy and monoclonal antibodies. However, ibrutinib is unique because it specifically targets the Bruton's tyrosine kinase (BTK) enzyme, which is crucial for the survival and proliferation of cancer cells. By inhibiting BTK, ibrutinib disrupts the signaling pathways that CLL cells rely on, potentially leading to more targeted and effective treatment. Researchers are excited about ibrutinib because it offers a non-chemotherapy option with a different mechanism of action, which can result in fewer side effects and improved outcomes for patients.

What evidence suggests that ibrutinib might be an effective treatment for chronic lymphocytic leukemia?

Research has shown that ibrutinib, the treatment under study in this trial, effectively treats chronic lymphocytic leukemia (CLL). In one study, 96.8% of patients responded to ibrutinib, with 40.7% achieving a complete response and 56.1% a partial response. Specifically, the RESONATE-2 study found that patients experienced lasting survival benefits, with the disease not worsening for nearly 9 years on average. These results suggest that ibrutinib can significantly slow CLL by blocking the enzymes cancer cells need to grow. Overall, ibrutinib has proven to be a promising treatment for CLL, with strong evidence from real-world data supporting its effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Sikander Ailawadhi

Principal Investigator

Mayo Clinic

Asher Chanan-Khan, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with chronic lymphocytic leukemia (CLL) who have had some response to initial cancer treatment but still have residual disease. They must understand the study and consent, not be nursing or pregnant, and can't join if they've had certain other cancers, are MRD-negative after frontline therapy, need strong CYP3A modulators, or have serious liver impairment.

Inclusion Criteria

Understand and voluntarily sign an informed consent form

I've completed at least 2 cycles of initial treatment for CLL and responded to it, but haven't had ibrutinib.

I have a type of leukemia and still have some cancer cells despite treatment.

Exclusion Criteria

I am of childbearing age and do not plan to use birth control.

I haven't used any experimental drugs in the last 28 days, except for low dose prednisone.

You have other health conditions that could make it unsafe for you to take ibrutinib, such as HIV infection or bleeding disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily on days 1-28, with treatment repeating every 4 weeks for up to 36 courses

144-148 weeks

Monthly visits for each treatment cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib

Trial Overview The trial tests Ibrutinib's effectiveness in treating minimal residual disease in CLL patients post front-line therapy. It aims to see if Ibrutinib can halt cancer growth by inhibiting enzymes needed for cell proliferation. Participants will also provide samples for laboratory biomarker analysis.

How Is the Trial Designed?

Group I: Treatment (ibrutinib) Experimental Treatment 2 Interventions

Patients receive ibrutinib PO QD on days 1-28. Treatment repeats every 4 weeks\* for up to 36 courses in the absence of disease progression or unacceptable toxicity. Note: \*The last course may last up to 56 days to accommodate the study drug discontinuation visit.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

In a study of 205 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib, the overall survival rate at 12 months was 88.8%, and the progression-free survival rate was 86.3%, indicating that ibrutinib is effective in a real-world setting.

However, 97.6% of patients experienced at least one adverse event, with 48.8% having severe (grade ≥3) events, and 42% discontinued treatment, primarily due to these adverse effects, suggesting that while ibrutinib is effective, its safety profile may lead to higher discontinuation rates compared to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib. Aarup, K., Rotbain, EC., Enggaard, L., et al.[2021]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is an effective treatment for chronic lymphocytic leukemia (CLL) and is generally well tolerated, even in older patients or those unable to undergo traditional chemotherapy.

However, adverse events, such as lymphocytosis and potential drug interactions, can lead to treatment interruptions and complications like major hemorrhage and atrial fibrillation, highlighting the need for careful monitoring and possible dose adjustments when used with certain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping a balance in chronic lymphocytic leukemia (CLL) patients taking ibrutinib: ibrutinib-associated adverse events and their management based on drug interactions. Cho, HJ., Baek, DW., Kim, J., et al.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Ibrutinib, a BTK inhibitor, has been shown to significantly improve clinical outcomes for patients with chronic lymphocytic leukemia, as demonstrated in two phase III trials.

When used alone or in combination with rituximab, ibrutinib enhances progression-free survival compared to traditional chemoimmunotherapy regimens, suggesting it should be considered a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Ibrutinib Confirmed for CLL. [2019]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3801/537228/Real-world-survival-outcomes-in-first-line

Real-world survival outcomes in first-line ibrutinib-treated ... The mean time from first observed diagnosis to 1L ibrutinib initiation was 38.0 (SD, 45.3) months among patients with high-risk CLL/SLL and 68.3 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11971162/

Final results on effectiveness and safety of Ibrutinib in patients ... 3). By 60 months, 96.8% of the retrospective patients had a response to ibrutinib treatment: 40.7% had a complete response and 56.1% a partial ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36534239/

Systematic Literature Review of Real-World Effectiveness ... This systematic literature review confirms the benefit of ibrutinib as a first-line treatment in patients with chronic lymphocytic leukemia in real-world ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2024.2402814

Real-world outcomes following ibrutinib dose reduction in ... Systematic literature review of real-world effectiveness results data for first-line ibrutinib in chronic lymphocytic leukemia and small lymphocytic lymphoma.

5. ashpublications.org ashpublications.org/blood/article/146/18/2168/546415/Final-analysis-of-the-RESONATE-2-study-up-to-10

Final analysis of the RESONATE-2 study: up to 10 years of ... Key PointsIn the final analysis of RESONATE-2, survival and PFS benefits of ibrutinib treatment were sustained, with median PFS reached at 8.9 years.Ibruti.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40413564/

Real-World Safety Profile of Ibrutinib in Chronic ... The overall response rate was 82.2%, with 42.2% achieving complete remission. Multivariate analysis identified age and comorbidities as ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38342972/

Outcomes with ibrutinib in patients with chronic lymphocytic ... The REALITY study provides further evidence of the effectiveness and safety of ibrutinib in patients with CLL in a real-world setting, particularly in earlier ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6550/501342/Real-World-Effectiveness-and-Safety-of-Ibrutinib

Real-World Effectiveness and Safety of Ibrutinib in Patients ... In this Belgian real-world study, ibrutinib was found to be an effective treatment for patients with CLL, including those with higher risk mutations, several ...

9. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/findings-from-landmark-resonate-2-study-confirm-sustained-survival-benefit-of-imbruvica-ibrutinib-for-first-line-chronic-lymphocytic-leukaemia-treatment-with-up-to-10-years-follow-up

Findings from landmark RESONATE-2 study confirm ... Ibrutinib was well tolerated as a long-term treatment and no new safety signals emerged. 1 Rates of adverse events (AEs) of interest during years 8–9 and 9–10 ...