Nivolumab Maintenance in Newly Diagnosed PCNSL With Persistent CSF Circulating Tumor DNA After Completion of First-Line Chemotherapy

NCT04401774 | Completed Phase 2 FDA Drug

• 1 other identifier: 19-383
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this additional part of the study is to test whether the study drug, nivolumab, is a safe treatment that will prevent participants' primary central nervous system lymphoma (PCNSL) from growing again (recurrence). Participants will be people with PCNSL who continue to have cell free tumor DNA (cfDNA) in their CSF despite completion of their first treatment (first-line treatment).

Conditions

Primary Central Nervous System Lymphoma (PCNSL)

Keywords

Nivolumab; Persistent Circulating Tumor DNA; Methotrexate-Based First-Line Induction Chemotherapy; 19-383

Outcome Measures

Primary Outcomes (2)

• Frequencies of toxicities

  Frequencies of toxicities will be summarized based on the Common Toxicity Criteria (CTCAE) version 5.0. Adverse events.

  within 60 days of therapy

• cfDNA conversion rate in CSF

  Conversion rate is defined as the proportion of patients receiving maintenance nivolumab who have undetectable cfDNA at one-year from the start of nivolumab maintenance.

  12 months

Study Arms (1)

Nivolumab Maintenance

EXPERIMENTAL

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.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab will be given every 4 weeks at 480mg flat dose intravenously for one year (total of 13 nivolumab doses).

Nivolumab Maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biospecimen and Data Collection:
• Histologically documented PCNSL with the ability to submit up to 20 unstained formalinfixed, paraffin embedded (FFPE) slides from the initial tissue diagnosis prior to study registration or histologically confirmed lymphomatous involvement of the CSF and/or eye/vitreous
• Patients must be able to tolerate MRI/CT scans with \[18F FDG\]
• Patients must be able to tolerate lumbar punctures and/or Ommaya taps
• Additional Criteria for Nivolumab Maintenance Arm:
• All criteria in the above "Biospecimen and Data Collection" section must be satisfied as well as:
• Persistent cfDNA in the CSF
• Participants must be able to understand and be willing to sign a written informed consent document
• Women and men who are at least 18 years of age on the day of consenting to the study
• KPS ≥60
• Life expectancy of \> 3 months (in the opinion of the investigator)
• Participants must have adequate bone marrow and organ function shown by:
• Absolute neutrophil count (ANC) ≥ 0.75 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L and no platelet transfusion within the past 21 days prior to study registration
• Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 21 days prior to study registration

You may not qualify if:

• Biospecimen and Data Collection:
• Patients with recurrent/refractory PCNSL. Patients with stable disease as their best response to first-line chemotherapy will also come off study.
• Patient with systemic, non-CNS lymphoma metastatic to the CNS
• Patient is known to have human immunodeficiency virus (HIV) infection
• Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
• Patient's who are planned to undergo consolidation with autologous HSCT
• Additional Criteria for Nivolumab Maintenance Arm:
• None of the criteria in the above "Biospecimen and Data Collection" section can be present. The following criteria must also not be present:
• Patient has undergone prior allogenic stem cell transplant
• Patient's who are planned to undergo consolidation with autologous HSCT
• Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 14 days of the first dose of study drug
• Patient is allergic to components of the study drug
• Patient is concurrently using other approved or investigational antineoplastic agents
• Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent
• Patient has an active concurrent malignancy requiring active therapy

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Grommes, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The phase II nivolumab maintenance trial is an open-label trial for patients who have completed high-dose methotrexate-based first-line chemotherapy for primary central nervous system lymphoma (PCNSL) but have persistent cfDNA in their CSF after treatment despite imaging response.

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 26, 2020
• Study Start: May 22, 2020
• Primary Completion: January 22, 2026
• Study Completion: January 22, 2026
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (7)