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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects and how well ibrutinib works in treating patients with chronic lymphocytic leukemia who responded to initial treatment used to reduce a cancer (front-line therapy) but have residual disease. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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.

What data supports the effectiveness of the drug Ibrutinib for treating chronic lymphocytic leukemia?

Ibrutinib has been shown to significantly improve progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse), response rate, and overall survival in patients with relapsed or refractory chronic lymphocytic leukemia. It is also effective in patients with specific genetic mutations, like chromosome 17 deletion, and has an acceptable safety profile with most patients tolerating the drug well. ^{1 2 3 4 5}

Is ibrutinib safe for treating chronic lymphocytic leukemia?

Ibrutinib, also known as Imbruvica, has been shown to have an acceptable safety profile in clinical trials for chronic lymphocytic leukemia, with less than 10% of patients stopping treatment due to side effects. However, real-world data indicates that some patients may experience adverse events like atrial fibrillation (irregular heartbeat), leading to treatment discontinuation. ^{1 2 4 6 7}

How is the drug Ibrutinib unique for treating chronic lymphocytic leukemia?

Ibrutinib is unique because it is a once-daily oral medication that specifically targets and blocks Bruton's tyrosine kinase, a protein that helps cancer cells grow, making it different from traditional chemotherapy. It is effective even for patients who are older or not fit for conventional treatments. ^{1 2 5 8 9}

Research Team

Sikander Ailawadhi

Principal Investigator

Mayo Clinic

Asher Chanan-Khan, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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, 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]

References

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. [2022]

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

Ibrutinib Treatment in Early Stage CLL Prolongs Time to Active Disease. [2022]

4. France pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Descriptive analysis of dosing and outcomes for patients with ibrutinib-treated relapsed or refractory chronic lymphocytic leukemia in a Canadian centre. [2021]

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

Real-world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib. [2021]

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

Safety and efficacy analysis of long-term follow up real-world data with ibrutinib monotherapy in 58 patients with CLL treated in a single-center in Greece. [2021]

8. England 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. [2021]

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

First-Line Ibrutinib Confirmed for CLL. [2019]