Ibrutinib for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kami Maddocks, MD

Must not be taking: Warfarin, Heparin, CYP3A4/5 inhibitors

Disqualifiers: Secondary malignancy, Cardiovascular disease, 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: 2

Duration: Indefinite as long as clinical benefit is derived

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II, single institution open-label, non-randomized monotherapy study to evaluate the clinical efficacy and durable disease control of PCI-32765 administered to patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having deletion 17p13 independently evaluated.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but you cannot have had chemotherapy, radiotherapy, or immunotherapy within 4 weeks before starting the study drug. If you're on corticosteroids, doses over 20 mg of prednisone per day require a 1-week break before starting 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 has an impressive overall response rate of 68% in patients with relapsed/refractory mantle cell lymphoma, and it is considered an emerging treatment option for B-cell malignancies due to its efficacy and tolerability. ^{1 2 3 4 5}

Is ibrutinib safe for humans?

Ibrutinib, also known as Imbruvica, has been shown to have an acceptable safety profile in clinical trials for chronic lymphocytic leukemia (CLL) and other B-cell malignancies. While some patients may experience side effects like atrial fibrillation (irregular heartbeat), less than 10% of patients stopped treatment due to adverse events. ^{1 3 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 effective for chronic lymphocytic leukemia. It is well tolerated by older patients and those who cannot undergo traditional chemotherapy. ^{2 3 4 8 9}

Research Team

Kami Maddocks, MD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for adults with relapsed or refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia who have failed at least one prior therapy. They should be in relatively stable condition (ECOG <=2), have a life expectancy over 2 months, and normal organ function as defined by specific blood test levels.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My CLL/SLL has come back or didn't respond to treatment, and I've tried at least one therapy.

I agree to use birth control during and for 30 days after the study if I can have children.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PCI-32765 (Ibrutinib) orally once daily at a dose of 420 mg for 28-day cycles. Weekly monitoring during the first month followed by monthly evaluations for 2 additional months, then every 3 months.

Indefinite as long as clinical benefit is derived

Weekly visits during the first month, monthly for 2 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life assessments and adverse event monitoring.

Up to 2 years post-treatment

Extension

Participants may continue receiving the study drug as long as they are deriving clinical benefit and not experiencing unacceptable toxicity.

Long-term

Treatment Details

Interventions

• Ibrutinib

Trial Overview The study tests the effectiveness of Ibrutinib (PCI-32765) on its own in patients with certain types of leukemia and lymphoma that haven't responded to previous treatments. It's an open-label Phase II trial where everyone gets the drug; there's no comparison group.

Participant Groups

Group I: Treatment (ibrutinib) Experimental Treatment 3 Interventions

Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy.

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?

Kami Maddocks, MD

Lead Sponsor

Trials

3

Recruited

220+

Kami Maddocks

Lead Sponsor

Trials

4

Recruited

220+

Findings from Research

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 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]

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. France pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

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

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

Ibrutinib: first global approval. [2022]

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

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

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]