Ibrutinib for Relapsed or Refractory Follicular Lymphoma

Not currently recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/5 inhibitors

Disqualifiers: CNS involvement, HIV, Hepatitis, 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: Unknown

Duration: Up to 5 courses (20 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ibrutinib, a medication that may stop the growth of cancer cells, for individuals with follicular lymphoma that has returned or is unresponsive to treatment. The trial aims to assess how well ibrutinib controls the disease when other treatments have failed. Participants will take ibrutinib daily in cycles, as long as it remains safe and effective. This trial suits those diagnosed with follicular lymphoma that has returned or worsened after previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that you stop taking any strong inhibitors or inducers of CYP3A4/5 enzymes and discontinue warfarin or similar vitamin K antagonists at least 28 days before starting. If you're on antiretroviral therapy for HIV, you may not be eligible unless specific conditions are met.

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

Research has shown that ibrutinib has been tested for safety and effectiveness in people with follicular lymphoma. One study found that 63% of patients who took ibrutinib responded positively, indicating it can help treat the disease. Another study examined patients with relapsed or hard-to-treat follicular lymphoma, similar to those in this trial, and assessed the safety of ibrutinib. These studies generally found that most patients tolerate ibrutinib well.

Although some patients experienced side effects, the treatment was manageable and did not cause serious problems for most. Common side effects were mild to moderate and could usually be treated. This suggests that ibrutinib is safe for many people with this type of lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for follicular lymphoma, which often involve chemotherapy and immunotherapy, ibrutinib offers a unique approach by targeting a specific protein called Bruton's tyrosine kinase (BTK). This mechanism of action helps interrupt the signaling pathways that cancer cells use to grow and survive. Researchers are excited about ibrutinib because it provides a targeted therapy option that potentially has fewer side effects than traditional treatments. Additionally, its oral administration makes it a more convenient choice for patients compared to intravenous therapies.

What evidence suggests that ibrutinib might be an effective treatment for follicular lymphoma?

Research has shown that ibrutinib, the treatment under study in this trial, can help treat follicular lymphoma, especially when other treatments fail. In one study, patients treated with ibrutinib went over three years on average without disease progression. Another study found that 63% of patients responded to the treatment, and 21% had a complete response, meaning their cancer was no longer detectable. These results suggest that ibrutinib may benefit those with relapsed or difficult-to-treat follicular lymphoma. ^{1 3 6 7 8}

Who Is on the Research Team?

Nancy L Bartlett

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or unresponsive follicular lymphoma, who've had at least one prior treatment. They must have measurable disease, acceptable blood counts and organ function, and be willing to provide samples for research. Pregnant women, those on certain drugs like CYP3A4/5 inhibitors or steroids, HIV-positive patients on antiretroviral therapy, individuals with active hepatitis B/C or other serious health issues are excluded.

Inclusion Criteria

My lymphoma is confirmed as follicular, grades 1, 2, or 3a.

I have a tumor or lymph node that is at least 1.5 cm big.

Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)

Exclusion Criteria

I haven't had chemotherapy or systemic therapy in the last 4 weeks.

I have not had a stroke or brain bleed in the last 6 months.

I need blood thinners like warfarin.

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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 5 courses (20 weeks)

Monthly visits for each course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 3 months until progressive disease, then every 6 months for 5 years.

5 years

Quarterly visits initially, then biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib

Trial Overview The trial tests Ibrutinib's effectiveness in treating follicular lymphoma that has returned after treatment or hasn't responded to previous treatments. It involves taking Ibrutinib pills which may block enzymes that cancer cells need to grow.

How Is the Trial Designed?

Group I: Treatment (ibrutinib) Experimental Treatment 2 Interventions

Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease at the end of course 2 may continue on therapy until the end of course 5 at the discretion of the treating physician.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5757691/

Single-agent ibrutinib in relapsed or refractory follicular ... Preliminary results of the DAWN study, a phase 2 study of ibrutinib in patients with chemoimmunotherapy-refractory FL, showed a significantly lower response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10709678/

Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in ... A prespecified analysis of the 347 patients with FL showed that median PFS was 38.4 months (95% CI, 24.18-49.35) in the ibrutinib + CIT arm and 20.6 months (95% ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01779791?term=Imbruvica&rank=7

A Study of PCI-32765 (Ibrutinib) in Patients With Refractory ... The purpose of this study is to evaluate the efficacy and safety of PCI-32765 ( ibrutinib ) administered to patients with chemoimmunotherapy-resistant ...

4. ashpublications.org ashpublications.org/blood/article/146/15/1782/546730/Treatment-of-relapsed-and-refractory-follicular

Treatment of relapsed and refractory follicular lymphoma A 5-year update demonstrated 5-year OS rates for R2 vs rituximab of 83.2% (95% confidence interval [CI], 76.3-88.3) vs 77.3% (95% CI, 70.1-83.1) ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025001284

Ibrutinib and Venetoclax in Relapsed and Refractory ... Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression- ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2473952923005037

Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in ... Six patients from each group reported transformation to diffuse large B-cell lymphoma. Median PFS was 40.5 months in the ibrutinib + CIT arm vs ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29851546/

Ibrutinib as Treatment for Patients With Relapsed/ ... The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients.

8. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00128-4/abstract

Ibrutinib and Venetoclax in Relapsed and Refractory ... Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median ...