Nivolumab Maintenance for Central Nervous System Lymphoma

Not currently recruiting at 7 trial locations

Overseen By Christian Grommes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticancer antibodies, Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug nivolumab (Opdivo) can safely prevent the recurrence of primary central nervous system lymphoma (PCNSL), a cancer affecting the brain and spinal cord. The focus is on individuals who still have cancer DNA in their spinal fluid after their first treatment. Participants must have completed their initial treatment for PCNSL and continue to show cancer DNA in their cerebrospinal fluid. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use certain medications like systemic immunosuppressants or be on high doses of corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that nivolumab may help treat relapsed or hard-to-treat primary central nervous system lymphoma (PCNSL). Some studies have found that nivolumab can lead to a strong and lasting improvement in some patients with this condition.

In one study, when combined with another drug, 78% of patients responded positively to nivolumab, and half of them experienced a complete response, meaning no signs of cancer were found. This suggests that nivolumab is generally well-tolerated and can be effective in managing this type of lymphoma.

While these results are promising, the current trial is in an early stage. Researchers are still learning about its safety and effectiveness for this specific use. However, nivolumab is already approved for other conditions, which provides some reassurance about its safety. Always consult healthcare professionals to understand more about the potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it offers a new way to maintain remission in central nervous system lymphoma by enhancing the body's own immune response. Unlike traditional chemotherapy that directly attacks cancer cells, nivolumab works by inhibiting the PD-1 protein on immune cells, effectively unleashing them to recognize and destroy cancer cells more effectively. Researchers are excited about nivolumab because it could provide a more targeted and potentially less toxic approach compared to conventional treatments like high-dose methotrexate. This immunotherapy approach could lead to better outcomes for patients who have persistent cancer indicators even after initial chemotherapy.

What evidence suggests that nivolumab might be an effective treatment for primary central nervous system lymphoma?

Research shows that nivolumab might help treat primary central nervous system lymphoma (PCNSL), especially when the disease returns or doesn't respond to other treatments. Earlier studies found that nivolumab can provide a lasting response for these patients. In one study, combining nivolumab with another drug led to a 78% response rate, meaning most patients saw their tumors shrink or stop growing. Additionally, 58% of patients experienced no disease progression for at least a year, known as the one-year progression-free survival (PFS) rate. In this trial, patients with persistent cfDNA in the CSF after first-line chemotherapy and either complete or partial response on imaging will enroll in the nivolumab maintenance treatment arm. These results suggest that nivolumab could be a promising option for managing PCNSL. ^{1 4 6 7 8}

Who Is on the Research Team?

Christian Grommes, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with primary central nervous system lymphoma (PCNSL) who still have tumor DNA in their spinal fluid after first-line treatment. They must be over 18, have a life expectancy of more than 3 months, and adequate organ function. Women must use birth control and have a negative pregnancy test; men also need to commit to using contraception.

Inclusion Criteria

I can care for myself but may need occasional help.

I can undergo spinal taps or Ommaya reservoir procedures.

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

Exclusion Criteria

I am unable to participate in all required study activities due to my health.

I do not have a severe illness or condition that could risk my safety in the study.

I haven't taken immunosuppressants or more than 5 mg/day of prednisone for the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

First-line Chemotherapy

Participants receive methotrexate-based first-line induction chemotherapy

Varies

Multiple visits (in-person)

Nivolumab Maintenance

Participants with persistent cfDNA in CSF receive nivolumab to prevent recurrence of PCNSL

12 months

Regular visits for CSF and blood collection, MRI imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The trial is testing Nivolumab as a maintenance therapy for PCNSL patients who've completed initial chemotherapy but still show tumor DNA in their spinal fluid. The goal is to see if Nivolumab can prevent the cancer from returning.

How Is the Trial Designed?

Group I: Nivolumab Maintenance Experimental Treatment 1 Intervention

All patients will undergo cerebrospinal fluid (CSF) and blood collection as well as MRI imaging as standard of care prior to (- 21 days) first-line treatment initiation, during first-line therapy (before initiation of the 5th methotrexate dose (+/- 7 days)), at completion of first-line chemotherapy therapy (+/- 7 days) as well as 60, 180, and 360 days after enrollment into maintenance or observation (+/- 7 days). Those patients with persistent cfDNA in the CSF after completion of first-line chemotherapy and either complete or partial response on imaging will be enrolled into the nivolumab maintenance treatment arm. All other patients (no persistent cfDNA in the CSF and either complete or partial response on imaging) are followed with observation. Patients who do not respond to first-line therapy are not eligible for nivolumab maintenance and will no longer be followed in the biospecimen and clinical data collection cohort.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

A case study of a 59-year-old woman with treatment-resistant laryngeal cancer revealed that nivolumab, an immunotherapy drug, can cause severe central nervous system (CNS) toxicities, specifically acute demyelinating encephalitis, which is rarely reported in the literature.

The patient's symptoms improved significantly after discontinuing nivolumab and receiving high-dose steroids and immunoglobulin therapy, suggesting that CNS toxicity from immune checkpoint inhibitors may be reversible with prompt treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. Zafar, Z., Vogler, C., Hudali, T., et al.[2020]

Nivolumab, an immune checkpoint inhibitor approved for non-small cell lung cancer, can cause rare but serious side effects like immune-related encephalitis in 1% to 3% of patients, highlighting the need for awareness among healthcare providers.

In a case study of a 74-year-old male with stage 4 lung cancer, early recognition and treatment with intravenous steroids led to significant recovery from nivolumab-induced encephalitis, emphasizing the importance of prompt management to reduce risks of severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. Richard, K., Weslow, J., Porcella, SL., et al.[2018]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

In a study of 40 patients with advanced non-small cell lung cancer treated with nivolumab, 22.5% experienced thyroid function changes, including hypothyroidism and hyperthyroidism, highlighting the need for regular monitoring of thyroid health during treatment.

Despite the occurrence of thyroid-related immune adverse events, 62.5% of patients showed a positive response to nivolumab after a median follow-up of 7.6 months, indicating that while endocrine IRAEs are common, they do not necessarily correlate with treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced thyroid dysfunction in patients with lung cancer. Ramos-Levi, AM., Rogado, J., Sanchez-Torres, JM., et al.[2021]

Nivolumab treatment resulted in an increased overall survival rate of 7.5 months compared to 5.1 months for the control group, indicating its efficacy in extending life for patients.

Patients receiving nivolumab also reported a better quality of life, suggesting that the treatment not only prolongs survival but also improves the well-being of those undergoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

In a Phase II study involving 18 patients with leptomeningeal disease, the combination of ipilimumab and nivolumab showed promising efficacy, with 44% of patients alive at three months, surpassing the expected 18%.

The treatment had an acceptable safety profile, although one-third of patients experienced significant adverse events, including two cases leading to treatment discontinuation due to hepatitis and colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. Brastianos, PK., Strickland, MR., Lee, EQ., et al.[2021]

In a retrospective study of five patients with advanced non-small cell lung cancer (NSCLC) and new or progressing brain metastases, nivolumab showed promising intracranial activity, with one complete and one partial response observed, and stabilization of leptomeningeal carcinomatosis in another patient.

Nivolumab was well-tolerated, with no severe treatment-related adverse events reported, suggesting a favorable safety profile for patients with CNS metastases from NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. Dudnik, E., Yust-Katz, S., Nechushtan, H., et al.[2022]

In a study involving 51 patients with newly diagnosed advanced-stage classic Hodgkin lymphoma, nivolumab followed by a combination therapy (N-AVD) showed an impressive objective response rate of 84%, with 67% of patients achieving complete remission.

The treatment was generally well-tolerated, with 59% of patients experiencing grade 3 to 4 treatment-related adverse events, but most were manageable, and the 9-month modified progression-free survival rate was 92%, indicating strong efficacy and safety for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. Ramchandren, R., Domingo-Domènech, E., Rueda, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12016817/

Nivolumab in Relapsed or Refractory Primary Central Nervous ... Our study suggests that nivolumab can be a reasonable option with the durable response for RR PCNSL.

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1772/503252/Nivolumab-in-Relapsed-or-Refractory-Primary-CNS

Nivolumab in Relapsed or Refractory Primary CNS Lymphoma The median overall survival (OS) was 18.9 months (95% CI, 5.0 - 32.8), and the 1-yr OS rate was 53.1% (± 13.9%). As expected, responders showed ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925000795

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.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)05074-3/fulltext

Primary central nervous system lymphomas: EHA–ESMO ... The treatment resulted in a 1-year PFS rate of 58% and a 3-year OS rate of 61%, without significant differences between the two induction arms.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5766844/

PD-1 blockade with nivolumab in relapsed/refractory primary ... Our data suggest that nivolumab is active in relapsed/refractory PCNSL and PTL and support further investigation of PD-1 blockade in these diseases.

6. ashpublications.org ashpublications.org/bloodadvances/article/9/7/1485/535449/Phase-2-trial-of-ibrutinib-and-nivolumab-in

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.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-03899

Nivolumab for People with Newly Diagnosed Primary ... The purpose of this trial is to test whether the study drug, nivolumab, is a safe treatment that prevents patients' primary central nervous system lymphoma from ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123083246

Nivolumab and Ibrutinib for Treatment of Patients with ... Ibrutinib and Nivolumab resulted in significant clinical activity in patients with refractory/relapsed CNS lymphoma.