Nivolumab + Ibrutinib for CNS Lymphoma

Overseen By Jason Westin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: BTK inhibitors, PD1 inhibitors

Disqualifiers: Cardiovascular disease, Stroke, Autoimmune diseases, 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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two drugs, nivolumab and ibrutinib, in treating central nervous system lymphoma that has recurred or is resistant to other treatments. Nivolumab, an immunotherapy, helps the immune system target cancer cells, while ibrutinib (also known as Imbruvica) inhibits enzymes that promote cancer cell growth. The trial aims to determine if this combination is more effective against this type of cancer. Individuals whose central nervous system lymphoma has returned after at least one prior treatment may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on high-dose steroids or immune suppression medications unless they are stopped at least 3 days before starting the study drugs. Also, you cannot use warfarin, strong CYP3A inhibitors, or have recently received live vaccines.

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

Research has shown that using ibrutinib and nivolumab together is generally safe for people with central nervous system lymphoma. In a study with 18 patients, the treatment was well-tolerated, and some patients experienced cancer remission for over two years. Although side effects can occur, the overall safety is considered reasonable. This suggests that these two drugs together may offer a promising option for patients with difficult-to-treat lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nivolumab and ibrutinib for CNS lymphoma because these drugs offer a unique approach compared to traditional chemotherapy and radiation treatments. Nivolumab is an immunotherapy drug that works by helping the immune system recognize and attack cancer cells, while ibrutinib is a targeted therapy that blocks specific proteins involved in cancer cell growth. This combination aims to enhance the body's ability to fight cancer by both direct interference with cancer cell pathways and boosting the immune response, potentially leading to more effective and longer-lasting results than current standard treatments.

What evidence suggests that nivolumab and ibrutinib might be effective treatments for central nervous system lymphoma?

This trial will evaluate the combination of ibrutinib and nivolumab for treating central nervous system (CNS) lymphoma. Research has shown that using ibrutinib and nivolumab together may help treat CNS lymphoma. In one study, 78% of patients responded to this treatment, and in 50% of those cases, the cancer became undetectable. Some patients remained in remission for over two years. Ibrutinib blocks enzymes that cancer cells need to grow, while nivolumab helps the immune system fight the cancer. These results suggest that this combination can effectively manage CNS lymphoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory central nervous system lymphoma. Participants must have adequate organ function, not be pregnant or breastfeeding, agree to use effective contraception, and have had at least one prior systemic therapy. Excluded are those with uncontrolled conditions like hypertension, infections, certain cardiovascular diseases, autoimmune diseases, recent major surgeries or therapies.

Inclusion Criteria

Total bilirubin =< 1.5 x upper limit of normal (ULN). For patients with Gilbert's disease, total bilirubin up to =< 3 x ULN is allowed provided normal direct bilirubin

I can take care of myself and perform daily activities.

Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use a highly effective contraception method during the study and for 23 weeks following the last dose of the study drugs. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drugs. Men must agree not to donate sperm during and for 3 months after the last dose of study drug. Women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria

I have had lung inflammation or disease proven by biopsy that affected my lung function tests significantly.

I have not had a stem cell transplant in the last 6 months and do not have graft-versus-host disease.

Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure >= 160 mmHg or diastolic >= 100 mmHg)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ibrutinib daily and nivolumab bi-weekly for up to 6 courses, each lasting 28 days

24 weeks

Bi-weekly visits for nivolumab administration

Extension

Patients achieving at least a partial response may continue therapy for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Nivolumab

Trial Overview The study tests the effectiveness of combining two drugs: Nivolumab (an immunotherapy drug) and Ibrutinib (a drug that blocks enzymes needed for cell growth), in treating patients whose central nervous system lymphoma has returned after treatment or hasn't responded to previous treatments.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 2 Interventions

Patients receive ibrutinib PO daily on days 1-28 and nivolumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response after 6 courses may continue therapy for up to 2 years.

Group II: Cohort A Experimental Treatment 2 Interventions

Patients receive ibrutinib PO daily on days 1-28. Beginning course 1, patients also receive nivolumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response after 6 courses may continue therapy for up to 2 years.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39908461/

Phase 2 trial of ibrutinib and nivolumab in patients with ... We conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03770416

Study Details | NCT03770416 | Nivolumab and Ibrutinib in ... This phase II trial studies the side effects and how well nivolumab and ibrutinib works in treating patients with central nervous system lymphoma that has ...

3. cancernetwork.com cancernetwork.com/view/ibrutinib-nivolumab-shows-clinical-activity-in-r-r-cns-lymphoma

Ibrutinib/Nivolumab Shows Clinical Activity in R/R CNS ... Among 18 patients with central nervous system lymphoma treated with the ibrutinib/nivolumab combination regimen, 3 had remission beyond 2 years.

4. researchgate.net researchgate.net/publication/330342076_Safety_and_activity_of_ibrutinib_in_combination_with_nivolumab_in_patients_with_relapsed_non-Hodgkin_lymphoma_or_chronic_lymphocytic_leukaemia_a_phase_12a_study

Safety and activity of ibrutinib in combination with ... Combination ibrutinib and nivolumab therapy also showed promising results in patients with refractory or relapsed central nervous system ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985036/

Phase 2 trial of ibrutinib and nivolumab in patients with ... Ibrutinib and nivolumab showed a response rate of 78% and the best complete response rate was 50% for relapsed/refractory CNS lymphomas.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02940301

Ibrutinib and Nivolumab in Treating Patients With Relapsed ... This phase II trial studies how well ibrutinib and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back or has not ...