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

NCT04022980 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00081673Pro00036735LCI-HEM-PCNSL-RMPV-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief 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 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

Conditions

Brain and Nervous System; Eye and Orbit

Keywords

Lymphoma; Central Nervous System Malignancy

Outcome Measures

Primary Outcomes (2)

• 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

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

• 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)

  2 years

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Objective and Complete Response Rates

  approx. 2 years

• Conversion Rate from Partial to Complete Response

  approx. 2 years

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

  up to 30 days after last dose of Nivolumab

Study Arms (2)

Stage 1

EXPERIMENTAL

Safety Run-In

Drug: Nivolumab

Stage 2

EXPERIMENTAL

Expansion Cohort

Drug: Nivolumab

Interventions

Nivolumab DRUG

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

Stage 1; Stage 2

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Atrium Health Levine Cancer Institute: collaborator
• Wake Forest University Health Sciences: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Dana Farber Cancer Institute

Brookline, Massachusetts, 02215, United States

Location

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neurologic Manifestations; Lymphoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Steven Park, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 17, 2019
• Study Start: March 31, 2020
• Primary Completion: January 21, 2025
• Study Completion: December 22, 2025
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)