Nivolumab Maintenance for Central Nervous System Lymphoma

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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if nivolumab, a drug that boosts the immune system, can prevent the return of a specific brain cancer in patients who still show signs of cancer after their first treatment. Nivolumab has shown promising activity in various cancers.

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.

What data supports the effectiveness of the drug Nivolumab for Central Nervous System Lymphoma?

Nivolumab has shown effectiveness in treating other conditions, such as head and neck cancer and non-small cell lung cancer (NSCLC), where it improved survival and showed activity in the brain. In a study with NSCLC patients, some experienced positive responses in brain metastases, suggesting potential benefits for central nervous system conditions. ^{1 2 3 4 5}

Is nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, has been studied in many clinical trials for cancer treatment. Common side effects include fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects, though rare, can include immune-related issues like inflammation of the brain or blood disorders, but these are often reversible with treatment. ^{3 6 7 8 9}

How does the drug nivolumab differ from other treatments for central nervous system lymphoma?

Nivolumab is unique because it is an immune checkpoint inhibitor that works by enhancing the body's immune response against cancer cells, which is different from traditional chemotherapy that directly targets and kills cancer cells. It has shown potential intracranial activity in other cancers, like non-small cell lung cancer, suggesting it might be effective in treating central nervous system lymphoma, a condition with limited standard treatment options. ^{1 2 6 10 11}

Research Team

Christian Grommes, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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]

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]

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]

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 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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. [2021]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

Nivolumab-induced thyroid dysfunction in patients with lung cancer. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. [2018]