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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug ibrutinib for individuals with chronic lymphocytic leukemia (CLL) who have not responded to other treatments. Participants will take a daily pill, and researchers will monitor cancer response and any side effects. The trial is best suited for those diagnosed with CLL who have tried at least one other therapy without success. Regular check-ins will track the drug’s effects over time. As a Phase 2 trial, this research measures ibrutinib's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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 study involving 1,284 patients who used ibrutinib for over five years, it proved safe for long-term use. Most participants continued the treatment for an average of 51 months.

Another study from Belgium found ibrutinib effective and safe, even for those with high-risk genetic factors. This indicates that people with more challenging cases of CLL could still benefit from the treatment without major safety concerns.

Overall, evidence suggests that ibrutinib has a strong safety record. While it can cause side effects, most patients manage them well. Discussing potential risks and benefits with a healthcare provider is important before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ibrutinib is unique because it targets the Bruton’s tyrosine kinase (BTK) enzyme, which plays a crucial role in the survival and spread of cancer cells in chronic lymphocytic leukemia (CLL). Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, ibrutinib specifically blocks this enzyme, disrupting the cancer cell's communication and growth processes. Researchers are excited about ibrutinib because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients with CLL.

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, is highly effective for chronic lymphocytic leukemia (CLL). One study found that 96.8% of patients responded to ibrutinib, with 40.7% achieving a complete response and 56.1% a partial response. Long-term data indicates that ibrutinib can help patients live for a median of 8.9 years without cancer progression. Additionally, ibrutinib has proven significantly effective in high-risk CLL cases, extending patients' survival times. Overall, these findings strongly support ibrutinib as an effective treatment option for CLL. ^{6 7 8 9 10}

Who Is on the Research Team?

Kami Maddocks, MD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

Citations

1. 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 ...

2. 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 ...

3. targetedonc.com targetedonc.com/view/new-10-year-data-show-ibrutinib-s-lasting-efficacy-in-cll-sll

New 10-Year Data Show Ibrutinib's Lasting Efficacy in CLL ... After a median follow-up of 9.6 years for the ibrutinib arm, the final analysis revealed a median progression-free survival of 8.9 years for ...

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. imbruvicahcp.com imbruvicahcp.com/cll/efficacy/resonate-2/long-term-data

RESONATE-2 - Long-Term 8-Year Data - Imbruvica The estimated 18-month PFS rate in the primary analysis was 90% with IMBRUVICA® versus 52% with chlorambucil, hazard ratio 0.16, and IMBRUVICA® treatment led to ...

6. imbruvicahcp.com imbruvicahcp.com/cll/safety/pooled-long-term-safety

Pooled Long-Term Safety | IMBRUVICA® (ibrutinib) HCP The safety data from long-term treatment with IMBRUVICA® over 5 years of 1,284 patients were analyzed. The median treatment duration was 51 months (range, 0.2 ...

7. 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 ...

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

Real-World Safety Profile of Ibrutinib in Chronic ... Ibrutinib remains an effective treatment for lymphocytic leukemia, even in patients with comorbidities and high-risk genetic characteristics.

9. imbruvica.com imbruvica.com/cll

Chronic Lymphocytic Leukemia Treatment In one clinical trial of 269 people aged 65 and older with CLL or SLL who had not been treated before, people who took IMBRUVICA® had a 56% lower risk of death ...

10. news.abbvie.com news.abbvie.com/2020-12-06-Combined-Data-from-Multiple-Phase-3-Studies-of-IMBRUVICA-R-ibrutinib-Show-Efficacy-and-Safety-in-High-Risk-Previously-Untreated-Chronic-Lymphocytic-Leukemia-CLL-and-Real-World-Data-Indicating-Low-Biomarker-Testing-Rates-for-These-Patients

Combined Data from Multiple Phase 3 Studies of ... First-line treatment with IMBRUVICA-based therapies resulted in sustained, long-term efficacy with high 4-year PFS rates in high-risk CLL patients.