What side effects are associated with this type of intervention?

The most common treatments for Central Nervous System Lymphoma (CNSL) involving PD-1 inhibitors like Nivolumab are associated with several immune-related adverse events. These can include pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Severe side effects may also involve neurological complications such as myasthenia gravis, encephalitis, and aseptic meningitis. It is crucial to monitor patients closely for these toxicities and manage them promptly to mitigate risks.

What prior FDA approvals exist?

There is no specific mention of FDA-approved treatments for Central Nervous System Lymphoma involving PD-1 inhibitors like nivolumab in the provided context. However, nivolumab has shown promise in treating other types of lymphomas and cancers, and it is being studied for its efficacy in preventing recurrence in patients with PCNSL who have persistent cell-free tumor DNA after first-line chemotherapy. Broadly, PD-1 inhibitors such as nivolumab and pembrolizumab have been approved for various cancers, including melanoma and non-small cell lung cancer, due to their ability to enhance the immune system's response against tumor cells.

What other types of research exist?

Promising novel alternatives to Nivolumab for Central Nervous System Lymphoma patients include Pembrolizumab, which has shown potential in increasing progression-free survival (PFS) and overall survival (OS) in a small randomized surgical study. Further research and clinical trials are needed to validate these findings and explore additional options.

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Nivolumab Maintenance for Central Nervous System Lymphoma

Phase 2

Waitlist Available

Led By Christian Grommes, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

KPS ≥60

Patients must be able to tolerate lumbar punctures and/or Ommaya taps

Must not have

Life-threatening illness, medical condition, or organ system dysfunction that could compromise the subject's safety or put the study outcomes at undue risk

Patient with systemic, non-CNS lymphoma metastatic to the CNS

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Nivolumab may cause immune-related side effects such as inflammation of organs, skin rash, hormone gland problems (like thyroid), diarrhea or colitis, liver inflammation, and lung issues like pneumonitis.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can care for myself but may need occasional help.

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I can undergo spinal taps or Ommaya reservoir procedures.

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My blood counts and organ functions are within the required ranges for the study.

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My brain or spinal cord lymphoma diagnosis is confirmed, and I can provide tissue samples.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My lymphoma has spread to my brain or spinal cord.

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I have had a stem cell transplant from a donor.

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I am currently receiving treatment for another cancer.

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I am not pregnant or nursing.

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I have a history of hepatitis B or C.

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I am currently using other cancer treatments.

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I have an ongoing infection that is not under control.

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I have heart problems and abnormal EKG results.

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I have or had lung inflammation not caused by an infection.

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I am scheduled for a stem cell transplant using my own cells.

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I have been treated with specific immune therapy drugs before.

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My brain lymphoma has come back or didn't respond to first treatment.

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I need high doses of steroids daily to manage my condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequencies of toxicities

cfDNA conversion rate in CSF

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Nivolumab MaintenanceExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Central Nervous System Lymphoma (CNSL) include immune checkpoint inhibitors such as Nivolumab, which targets the PD-1 pathway. PD-1 is a protein on the surface of T-cells that, when engaged, inhibits the immune response. Tumors can exploit this pathway to evade immune detection. Nivolumab blocks PD-1, thereby enhancing the body's immune response against cancer cells. This mechanism is particularly important for CNSL patients as it offers a targeted approach to boost the immune system's ability to fight lymphoma within the central nervous system, potentially leading to better control of the disease and improved outcomes.