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Brain and Nervous SystemPhase 1NCT04022980

Nivolumab Consolidation in Older (≥ 65) Patients With Primary CNS Lymphoma

A Phase 1 study testing Nivolumab in people with Brain and Nervous System and Eye and Orbit, run by Wake Forest University Health Sciences at 4 sites 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

The primary objective of Stage 1 is to evaluate the safety of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in older subjects with PCNSL in terms of a tolerated dose (based on dose-limiting toxicities) for the expansion phase of the study (Stage 2).The primary objective of Stage… Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Brain and Nervous System, Eye and Orbit
What is being tested?
Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
4 sitesUnited States
Study dates
31 Mar 2020to 22 Dec 2025
Phase
Phase 1
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 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Subjects must meet all of the following criteria to participate in this study:
  • Written informed consent and HIPAA authorization for release of personal health information of subject or subject's legally authorized representative.
  • Age ≥ 65 years at the time of consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3 within 14 days prior to day 1 of treatment
  • Histological or cytological confirmation of PCNSL, CD20 positive by immunohistochemistry
  • Received at least 2 cycles of high-dose methotrexate (HD-MTX) containing induction chemotherapy per institutional standard (R-MPV preferred; see Appendix VI ) without evidence of progressive disease. HD-MTX is typically defined as a MTX dose of at least 3.0 g/m^2.
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  • Recovered from all reversible acute toxic effects of prior therapy (other than alopecia) to ≤ Grade 1 or baseline)
  • Measurable disease at the time of diagnosis (i.e. prior to pre-study HD-MTX containing induction chemotherapy) including lesions that can be accurately measured in 2 dimensions by CT or MRI of brain and with a greatest transverse diameter of ≥ 1 cm. The following disease assessments must have been obtained prior to initiation of pre-study HD-MTX containing induction chemotherapy: MRI of the brain with contrast (and spine with contrast if indicated)
  • Deemed poor candidate for whole brain irradiation (WBI) or autologous stem cell transplant (ASCT) due to advanced age, ECOG performance status of 2, or in the opinion of the treating physician, subject would not tolerate the administration of WBI or ASCT for other reasons
  • Life expectancy of at least 3 months
  • Demonstrate adequate organ function as defined below (all screening labs to be obtained within 14 days prior to day 1 of treatment):
  • Absolute Neutrophil Count (ANC) ≥ 1000K/mm3
  • Platelet Count ≥ 75 K/mm3
  • Hemoglobin (Hgb) ≥ 8 g/dL
  • Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 cc/minute as measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN)
  • Aspartate aminotransferase (AST) ≤ 3 x ULN
  • Alanine aminotransferase (ALT) ≤ 3 x ULN
  • Note: since subjects are not enrolled until study treatment is initiated, any labs drawn prior to initiating study treatment on Cycle 1 Day 1 need to meet eligibility criteria since the subject will still be in screening at the time of the lab draw.
  • Females of childbearing potential (FCBP) must have a negative serum pregnancy test within 3 days prior to day 1 of treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
  • FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) from the time of informed consent until 5 months after treatment discontinuation. Contraceptive methods with low user dependency are preferable but not required. (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)
  • As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Subjects must not meet any of the following criteria:
  • Documented or suspected ophthalmologic involvement at the time of enrollment as determined by the investigator. Subjects with ophthalmologic involvement prior to or during pre-study induction are allowed if there is no evidence of ophthalmologic involvement prior to enrollment as determined by the investigator.
  • Any concurrent systemic involvement by lymphoma outside CNS or intraocular lymphoma without evidence of brain disease
  • Any previous chemotherapy or radiation therapy for PCNSL except for treatment with a HD-MTX containing induction chemotherapy. Subjects treated with corticosteroids for PCNSL are allowed.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
  • Has a known additional malignancy within the past 5 years that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or carcinoma of the prostrate with a current PSA value of <0.5 ng/mL or other cancer for which subject has completed treatment, been disease-free for at least five years, and is considered by Sponsor-Investigator to be at <30% risk of relapse, or on hormonal therapy for a history of either prostate cancer or breast cancer, provided that there has been no evidence of disease progression during the previous three years.
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  • Treatment with any investigational drug (including drugs not FDA-approved for the indication for which they are given) within 28 days prior to day 1 of treatment
  • Subjects with active, uncontrolled infections (subjects must be afebrile for >48 hours off systemic antibiotics).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator.
  • Major surgery and/or radiotherapy within 14 days prior to initiation of study treatment
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
  • Active infectious hepatitis, type B or C. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) may be included if HBV DNA is undetectable.
  • Subjects with active interstitial pneumonitis.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana Farber Cancer Institute

    Brookline, Massachusetts, 02215

  • UNC Hospitals, The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • The University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1B Trial Nivolumab Consolidation Following Completion of High-Dose Methotrexate Containing Induction Chemotherapy in Older (≥ 65) Patients With Primary CNS Lymphoma

The primary objective of Stage 1 is to evaluate the safety of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in older subjects with PCNSL in terms of a tolerated dose (based on dose-limiting toxicities) for the expansion phase of the study (Stage 2).The primary objective of Stage 2 is to evaluate the efficacy of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in terms of the 2-year progression-free survival rate and compare to relevant historical controls

Read the detailed description

This is a 2-stage phase 1B study of nivolumab consolidation following completion of HD-MTX containing induction chemotherapy in older (≥ 65 years old) patients with previously untreated primary CNS lymphoma. Stage 1 is designed to evaluate the safety of nivolumab consolidation. We plan to use 3+3 design and start at the FDA approved single agent dose of nivolumab 480 mg intravenously every 4 weeks. Stage 2 is designed to evaluate the safety as well as efficacy of nivolumab consolidation after HD-MTX containing induction chemotherapy in an expansion cohort.

Being tested
Nivolumab
Keywords
Lymphoma, Central Nervous System Malignancy
Medical subject headings
Neurologic Manifestations, Lymphoma

What participants receive

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

  • NivolumabDrug

    HD-MTX containing induction chemotherapy (per standard of care) followed by Nivolumab consolidation.

Study groups in NCT04022980
Study groupRoleWhat they receive
Stage 1ExperimentalSafety Run-In
Receives: Drug: Nivolumab
Stage 2ExperimentalExpansion Cohort
Receives: Drug: Nivolumab

What is being measured

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

  1. Safety of Nivolumab in Older Subjects

    The primary endpoint for the Stage 1 phase of the study is dose-limiting toxicity which will be assessed for each Stage 1 subject using the DLT criteria

    Measured: Until up to 6 subjects can be adequately assessed for DLT.

  2. Efficacy of Nivolumab

    The primary endpoint for the Stage 1 phase of the study is the 2-year progression-free endpoint which will be determined for each subject as a binary variable indicating if they are alive and progression-free at 2 years (PFS2)

    Measured: 2 years

Secondary outcomes (6)

  1. Progression Free Survival (PFS)

    PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.

    Measured: 2 years

  2. Overall Survival (OS)

    OS is defined as the duration from enrollment to the date of death from any cause.

    Measured: 2 years

  3. Objective and Complete Response Rates

    Objective response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR or PR as determined by the International Criteria for PCNSL (IPCG). Complete response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR as determined by the International Criteria for PCNSL(IPCG).

    Measured: approx. 2 years

  4. Conversion Rate from Partial to Complete Response

    Response conversion will be determined for each subject who achieve a best overall response of PR during induction therapy as a binary variable indicating if the subsequently achieve a best overall response of CR to nivolumab consolidation therapy.

    Measured: approx. 2 years

  5. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Adverse events will be collected for each subject using NCI CTCAE v5.0 criteria. A binary variable will be determined for each subject indicating whether or not the subject experienced an AESI during treatment with nivolumab consolidation therapy, across any cycle nivolumab treatment administration.

    Measured: up to 30 days after last dose of Nivolumab

  6. Subset Analysis of 2 Year Progression Free Survival

    A subset analysis of the primary population will be performed on those members of the evaluable population for the primary objective completing at least two cycles of nivolumab. PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.

    Measured: 2 years

Timeline

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

  1. First posted17 Jul 2019
  2. Study start31 Mar 2020
  3. Primary completion21 Jan 2025
  4. Study completion22 Dec 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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04022980
Sponsor's protocol ID
IRB00081673
Other IDs
Pro00036735, LCI-HEM-PCNSL-RMPV-001
Status last verified
Dec 2025
First submitted
12 Jul 2019
Last updated
30 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab in people with Brain and Nervous System and Eye and Orbit, run by Wake Forest University Health Sciences at 4 sites 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 22 inclusion and 14 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 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Safety of Nivolumab in Older Subjects (time frame: Until up to 6 subjects can be adequately assessed for DLT.). The study lists 2 primary outcomes in all. 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 NCT04022980.

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 30 Dec 2025.

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