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Central Nervous System B-Cell Non-Hodgkin LymphomaPhase 2NCT03770416

Nivolumab and Ibrutinib in Treating Patients With Relapsed or Refractory Central Nervous System Lymphoma

A Phase 2 study testing Ibrutinib and Nivolumab in people with Central Nervous System B-Cell Non-Hodgkin Lymphoma and Recurrent Central Nervous System Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
15 Feb 2019to 10 Feb 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Relapsed refractory central nervous system lymphoma, pathology confirmed B cell lymphoma either by biopsy or by CSF review. Patient must previously have had at least one line of systemic therapy for CNS lymphoma.
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
  • Patients must have adequate renal and hepatic function
  • 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.
  • Serum creatinine ≤1.5 x ULN
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  • ALT and AST ≤3 x ULN
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (β-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.
  • Patients or their legally authorized representative must provide written informed consent.
  • Hematology values must be within the following limits:
  • Absolute neutrophil count (ANC) 1000/mm3 independent of growth factor support
  • Platelets 100,000/mm3 or 50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
  • Creatinine clearance (CrCl) > 30 ml/min

Who cannot join

  • History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses). If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center and after consultation with the Principal Investigator
  • Any major surgery or wound that has not healed, radiotherapy, cytotoxic chemotherapy, biologic therapy, immunotherapy, immunomodulatory drugs, experimental therapy within 4 weeks prior to the first dose of the study drugs.
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
  • History of stroke or cerebral hemorrhage within 6 months of enrollment.
  • Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg)
  • Prior history of BTK inhibitor or PD1 inhibitor prior to start of trial.
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  • Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring steroid therapy.
  • Patients with autoimmune diseases are excluded: Patients with a history of Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, Wegener's granulomatosis).
  • Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with active acute or chronic graft-versus host disease are excluded. Patients must be off immunosuppression for GVHD for at least 30 days before cycle 1 day 1.
  • Patients with organ allografts (such as renal transplant) are excluded.
  • History of biopsy proven interstitial lung disease or pneumonitis which has impacted PFT in a clinically significant manner.
  • Patients who are on high dose steroids (>10mg daily of prednisone or equivalent) or immune suppression medications. Note: Patients on high-dose steroids (doses >10mg/day of prednisone or equivalent) or immune suppression medications are eligible provided these drugs are discontinued at least 3 days prior to starting on the study drugs.
  • Patients with uncontrolled active infection (viral, bacterial, and fungal) are not eligible.
  • Active current hepatitis B or C infection/reactivation as measured by DNA/RNA quantification, or known seropositivity for HIV.
  • Patient is pregnant or breast-feeding.
  • Malabsorption syndrome or other condition that precludes enteral route of administration.
  • Concomitant use of warfarin or other Vitamin K antagonists.
  • Requires chronic treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see Appendix 3).
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.
  • Vaccinated with live, attenuated vaccines within 4 weeks of enrollment.
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Nivolumab and Ibrutinib for Relapsed or Refractory Central Nervous System Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the overall response rate of nivolumab and ibrutinib in central nervous system (CNS) lymphoma.

SECONDARY OBJECTIVES:

  1. Determine the overall response rate of 4 weeks of ibrutinib single agent in CNS lymphoma.

II. Determine the complete response rate of nivolumab and ibrutinib in CNS lymphoma.

III. Determine the 1-year progression free and overall survival outcomes in CNS lymphoma.

IV. Safety and toxicity of nivolumab and ibrutinib.

EXPLORATORY OBJECTIVES:

  1. Assess activation of T cells in peripheral blood and cerebrospinal fluid. II. Assess the cytokine profile from microglial cells in cerebrospinal fluid. III. Correlate features of peripheral blood T cell activation with toxicities. IV. Correlate features of peripheral blood T cell activation with response and progression free survival (PFS).
  2. Correlate baseline tumor characteristics with response and PFS. VI. Evaluate the ability of minimal residual disease testing to monitor response and differentiate from pseudo progression.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive ibrutinib orally (PO) daily on days 1-28. Beginning course 1, patients also receive nivolumab intravenously (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.

COHORT B: 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.

After completion of study treatment, patients are followed up within 3-4 weeks and then every 3 months for 2 years.

Being tested
Ibrutinib, Nivolumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT03770416
Study groupRoleWhat they receive
Cohort AExperimentalPatients 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.
Receives: Drug: Ibrutinib; Biological: Nivolumab
Cohort BExperimentalPatients 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.
Receives: Drug: Ibrutinib; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR)

    The overall response rate and its 95% confidence interval will be estimated. Fisher's exact test will be used to evaluate the association between response and other categorical patient variables.

    Measured: Up to 2 years

Secondary outcomes (4)
  1. ORR

    The overall response rate and its 95% confidence interval will be estimated. Fisher's exact test will be used to evaluate the association between response and other categorical patient variables.

    Measured: At 4 weeks of ibrutinib single agent

  2. Progression free survival (PFS)

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to objective disease progression or death from any cause, assessed at 1 year

  3. Overall survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to death, assessed at 1 year

  4. Incidence of adverse events (AEs)

    AE data will be summarized by frequency tables for all patients. For the toxicity endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

    Measured: Baseline up to 30 days after the last dose of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2018
  2. Study start15 Feb 2019
  3. Primary completion10 Feb 2025
  4. Study completion10 Feb 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03770416
Sponsor's protocol ID
2018-0510
Other IDs
NCI-2018-02181, 2018-0510
Status last verified
Feb 2025
First submitted
4 Dec 2018
Last updated
28 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chihara D, Steiner RE, Nair R, Feng L, Ahmed S, Strati P, Malpica L, Griffith DP, Mathew SA, Montinez W, Masand G, Samaniego F, Rodriguez MA, Hagemeister FB, Fayad LE, Iyer SP, Nastoupil LJ, Neelapu SS, Flowers CR, Westin JR. Phase 2 trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas. Blood Adv. 2025 Apr 8;9(7):1485-1491. doi: 10.1182/bloodadvances.2024014635.

    PubMed 39908461

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Nivolumab in people with Central Nervous System B-Cell Non-Hodgkin Lymphoma and Recurrent Central Nervous System Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03770416, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.

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