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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

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 come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab and ibrutinib may work better in treating patients with central nervous system lymphoma.

Research Team

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+