Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-HodgkinLymphomas

NCT03258567 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 17012517-C-0125
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The drug Nivolumab has been approved to treat some cancers. Researchers want to see if it can slow the growth of other cancers. They want to study its effects on cancers that may have not responded to chemotherapy or other treatments. Objectives: To see if Nivolumab slows the growth of some types of cancer or stops them from getting worse. To test the safety of the drug. Eligibility: People 12 and older who have Epstein-Barr Virus (EBV)-positive lymphoproliferative disorders or EBV-positive non-Hodgkin lymphomas with no standard therapy Design: Participants will be screened with: Medical history Physical exam Blood and urine tests CAT scan of the chest, abdomen, and pelvis Tumor and bone marrow biopsies (sample taken) Magnetic resonance imaging scan of the brain Lumbar puncture (also known as spinal tap) Positron emission tomography/computed tomography scan with a radioactive tracer Every 2 weeks, participants will get Nivolumab by vein over about 1 hour. They will also have: Physical exam Blood and pregnancy tests Review of side effects and medications During the study, participants will repeat most of the screening tests. They may also have other biopsies. After stopping treatment, participants will have a visit every 3 months for 1 year. Then they will have a visit every 6 months for years 2-5, and then once a year. They will have a physical exam and blood tests. ...

Conditions

Disorders, Lymphoproliferative; Epstein-Barr Virus Infections; Lymphoma; Lymphoproliferative Disorder

Keywords

Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• overall response rate of nivolumab in patients with EBV-positive LPD and EBV-positive NHL

  number of patients who respond to the protocol therapy (CR, PR, SD)

  one year

Secondary Outcomes (4)

• toxicity profile of nivolumab in patients with EBV-LPD

  4 weeks

• PFS of patients with EBV-LPD treated with nivolumab

  annually

• overall survival of patients with EBV-LPD treated with nivolumab

  annually

• duration of remission for patients who respond to nivolumab

  4 weeks

Study Arms (2)

Nivolumab (A)

EXPERIMENTAL

Nivolumab, 3mg/kg IV every 2 weeks for up to 2 years in subjects with responding disease with clinical benefit if they are tolerating treatment (closed effective with activation of Amendment C)

Biological: Nivolumab

Nivolumab (B)

EXPERIMENTAL

Nivolumab, 480 mg IV every 4 weeks for up to 2 years in subjects with responding disease with clinical benefit if they are tolerating treatment

Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

Nivolumab, 480 mg IV every 4 weeks for up to 2 years in subjects with responding disease with clinical benefit if they are tolerating treatment

Nivolumab (A); Nivolumab (B)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed EBV-positive LPD or an EBV-positive NHL confirmed by the Laboratory of Pathology, NCI.
• EBV-positive LPD. Subjects may be previously untreated or relapsed from prior therapy.
• Lymphomatoid granulomatosis (LYG), grades I-II
• Chronic active EBV disease (CAEBV) of B-cells or T-cells
• EBV-positive post-transplantation lymphoproliferative disorder (PTLD)
• NOTE: PTLD after solid organ transplantation is excluded. Patients who, at the discretion of the investigator, need urgent therapy with standard agents will not be eligible.
• EBV-positive B-cell NHL. Subjects must have relapsed from previous treatment with an anthracycline and rituximab-based regimen or be considered not eligible for the same.
• Lymphomatoid granulomatosis (LYG), grade III
• EBV-positive immunodeficiency-associated diffuse large B-cell lymphoma (DLBCL)
• EBV-positive DLBCL
• Subjects must be at least 2 weeks from prior anti-lymphoma therapy (including radiation therapy)
• Subjects must be at least 100 days from prior stem cell transplant (autologous or allogeneic) or Donor Lymphocyte Infusion (DLI)
• Age \>=12 years
• Patients \>= 12 and \< 18 years of age should weigh at least 40 kilograms (kg); there is no weight requirement for adult subjects.
• NOTE: If a pediatric patient is identified for possible enrollment who weighs less than 40 kg, the safety of the nivolumab dosing strategy used in this study must be discussed with the PI and manufacturer to confirm safety, and this discussion/approval for enrollment documented in the medical record prior to declaring the pediatric patient eligible.

You may not qualify if:

• Subjects who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• Subjects with second malignancies requiring active systemic therapy are excluded. Subjects with second malignancies not requiring active systemic therapy or pre-malignant conditions such as monoclonal B-cell lymphocytosis (MBL) or monoclonal gammopathy of undetermined significance (MGUS) may be eligible.
• Subjects with any condition or autoimmune disease that requires systemic corticosteroids (\> 10 mg daily prednisone equivalents) or immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted.
• Subjects with active graft-vs-host disease (GVHD) requiring steroids or other immunosuppressive agents; history of \>=grade II acute GVHD or extensive chronic GVHD.
• Subjects who have had solid organ transplant.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti CTLA-4 antibody.
• Non-oncology vaccine therapies for prevention of infectious disease within 4 weeks of study drug administration.
• A serious uncontrolled medical condition requiring therapy.
• Seizures disorder not controlled by anti-seizure medications.
• Subjects with CNS involvement may be included on the study as long as they have not had any seizure activity in past 4 weeks.
• Hepatitis B virus surface antigen positive.
• Active Hepatitis C infection with a positive PCR; subjects who are Hepatitis C antibody positive and PCR negative may be eligible. In these cases, the subjects will be monitored via HCV PCR throughout the study.
• History of anaphylactic reaction to monoclonal antibody therapy.
• HIV positive subjects are excluded because the function of their T-cell immune responses is impaired.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Lymphoma; Lymphoproliferative Disorders

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Neoplasms by Histologic Type; Neoplasms; 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

• Christopher J Melani, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Medical Oncology Referral Office

CONTACT

(240) 760-6050; ncimo_referrals@nih.gov

Christopher J Melani, M.D.

CONTACT

(240) 760-6057; christopher.melani@nih.gov

Study Design

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

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 23, 2017
• Study Start: April 26, 2018
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 29, 2026

Record last verified: 2026-02-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely. Genomic data will be available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data will be made available via dbGaP through requests to the data custodians.

Locations

US (1)