Ibrutinib +/− Rituximab for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Kinase inhibitors, Coumadin

Disqualifiers: Pregnancy, Severe infection, 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: 60

Duration: Up to 24 cycles (96 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for chronic lymphocytic leukemia (CLL) that has returned after prior treatments. It aims to determine if ibrutinib, a drug that may stop cancer cell growth, is more effective alone or when combined with rituximab, an immunotherapy that helps the immune system fight cancer. This trial may suit individuals previously treated for CLL or similar conditions who are experiencing symptoms again. Participants should not have undergone certain recent treatments or have other uncontrolled health issues. As a Phase 2 trial, the research focuses on measuring 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 requires that you stop certain treatments, like chemotherapy, high-dose corticosteroids, and some other therapies, at least 21 days before starting. If you're taking Coumadin, you need to stop it at least 7 days before the trial. For other medications, the protocol doesn't specify, so it's best to discuss with the trial team.

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

Research has shown that ibrutinib is generally well-tolerated by patients with chronic lymphocytic leukemia (CLL). In real-world studies, patients, including those with high-risk conditions, have responded well to the treatment. Most side effects are manageable, though some patients may experience mild to moderate issues.

Studies indicate that the combination of ibrutinib and rituximab can lead to faster remissions. Compared to other treatments, this combination has demonstrated better long-term results. While side effects can occur, the overall safety profile remains positive.

Both treatments have undergone thorough study, and evidence suggests they are safe for many patients. Those considering this trial should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Chronic Lymphocytic Leukemia (CLL) because they offer a novel approach compared to standard options like chemotherapy and monoclonal antibodies alone. Ibrutinib, a key player in this trial, is a Bruton's tyrosine kinase (BTK) inhibitor that specifically targets cancer cell growth pathways, potentially leading to more precise and effective treatment. When combined with rituximab, an antibody that helps the immune system identify and destroy cancer cells, the combo may enhance the overall therapeutic effect. This dual approach could offer improved outcomes with potentially fewer side effects than traditional CLL therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that ibrutinib, which participants in this trial may receive, effectively treats chronic lymphocytic leukemia (CLL). After five years, 96.8% of patients responded to ibrutinib, with 40.7% experiencing a complete response and 56.1% a partial response. In this trial, some participants will receive ibrutinib alone, while others will receive a combination of ibrutinib and rituximab. Combining ibrutinib with rituximab helps patients achieve faster remissions and reduces the amount of remaining disease. Long-term studies suggest that this combination can lead to longer periods without disease progression compared to other treatments. Overall, both ibrutinib alone and the ibrutinib-rituximab combination have proven very effective in managing CLL. ^{2 5 6 7 8}

Who Is on the Research Team?

Jan A. Burger

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed chronic lymphocytic leukemia who need treatment. They must be willing to use effective birth control and have no major health issues or recent treatments that could interfere. People with certain heart diseases, uncontrolled infections, bleeding disorders, or those pregnant/breastfeeding can't join.

Inclusion Criteria

I agree to use effective birth control during and 30 days after the study.

I haven't had cancer (except certain skin, cervix, or breast cancers) in the last 3 years.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

Investigational agent received within 30 days prior to the first dose of study drug

I haven't had cancer treatments like chemotherapy or immunotherapy in the last 21 days.

I haven't had major surgery or a serious injury in the last 28 days and don't expect to need major surgery during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ibrutinib orally once daily on days 1-28 of each cycle. In Arm II, patients also receive rituximab intravenously on specified days.

Up to 24 cycles (96 weeks)

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Follow-up at 60 days, then every 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Rituximab

Trial Overview The study is testing the effectiveness of Ibrutinib alone versus combined with Rituximab in patients whose chronic lymphocytic leukemia has returned after treatment. It aims to see if adding an immunotherapy agent (Rituximab) improves outcomes compared to just using a cell growth blocker (Ibrutinib).

How Is the Trial Designed?

Group I: Arm II (ibrutinib, rituximab) Experimental Treatment 4 Interventions

Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab IV over 3-8 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (ibrutinib) Experimental Treatment 3 Interventions

Patients receive ibrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 35.0 (SD, 48.0) and 64.4 (SD, 73.2) months for patients with high- ...

3. 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.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/ejh.14186

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 ...

5. 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.

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 ...