Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-HodgkinLymphomas
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|ClinicalTrials.gov Identifier: NCT03258567|
Recruitment Status : Recruiting
First Posted : August 23, 2017
Last Update Posted : May 30, 2018
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.
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.
People 12 and older who have Epstein-Barr Virus (EBV)-positive lymphoproliferative disorders or EBV-positive non-Hodgkin lymphomas with no standard therapy
Participants will be screened with:
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:
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.
|Condition or disease||Intervention/treatment||Phase|
|Epstein-Barr Virus Infections Lymphoma Lymphoproliferative Disorder Disorders, Lymphoproliferative||Drug: Nivolumab||Phase 2|
Expanded Access : National Cancer Institute (NCI) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
- Epstein-Barr virus (EBV) is a chronic viral infection associated with a heterogeneous group of lymphoproliferative disorders (LPD) and non-Hodgkin lymphomas (NHL)
- The shared pathobiology of EBV-positive LPDs and NHLs includes a defect in host mechanisms of immune tolerance and immunosurveillance.
- Programmed death-1 (PD-1) is a surface protein present on T cells, B cells, and macrophages that serves a co-inhibitory role to negatively regulate immune responses
- PD-1 and its ligands, PD L1 and PD-L2, are overexpressed in EBV-positive lymphomas and are markers of aggressive behavior.
- Blockade of the PD-1 pathway induces T-cell responses against tumor antigens in a variety of cancers, including Hodgkin lymphoma, that lead to clinical remissions.
- Nivolumab is a fully human IgG4 monoclonal anti-PD-1 receptor antibody with clinical activity in both indolent and aggressive lymphomas.
-To determine the best overall response rate of nivolumab in subjects with EBV-positive LPD and EBV-positive NHL
Subjects must have a confirmed diagnosis of an EBV-positive B-cell LPD or an EBVpositive NHL confirmed by Laboratory of Pathology, NCI
- Cohort 1: LPD subjects may be previously untreated or relapsed from prior therapy
- Cohort 2: 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.
Adequate bone marrow function (unless disease-related) defined as:
- Absolute neutrophil count greater than or equal to 750/mcL
- Hemoglobin greater than or equal to 9g/dL (transfusion permitted)
- Platelet count greater than or equal to 50,000/mcL (transfusion not permitted)
- Age greater than or equal to 12 years
- Phase II study of subjects with EBV-positive LPD and EBV-positive NHL, both relapsed and untreated.
- Subjects will be treated with nivolumab 3mg/kg IV every 2 weeks for up to 2 years if PR or SD with clinical improvement and no unacceptable toxicity and clinical benefit; subjects with CR will stop.
- All responding subjects (CR, PR, or SD with clinical benefit) who subsequently relapse or progress within 1 year after discontinuation of study drug are eligible for re-treatment.
- An optimal two-stage phase II trial design will be used to rule out a best overall response rate of 20% in each cohort. If fewer than 3 of the first 17 subjects respond, that cohort would accrue no more subjects.
- 37 subjects with EBV-positive LPD and 37 subjects with EBV-positive NHL will be enrolled on this protocol.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Trial of Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-HodgkinLymphomas|
|Actual Study Start Date :||April 26, 2018|
|Estimated Primary Completion Date :||September 1, 2022|
|Estimated Study Completion Date :||September 1, 2023|
nivolumab 3mg/kg via IV infusion over approximately 60minutes every 2 weeks for up to 1 year in subjects without unacceptable toxicity who achieve complete remission; and up to 2 years in subjects with partial response (PR) or stable disease (SD) with clinical benefit if they are tolerating nivolumab
3mg/kg via IV infusion over 30 minutes every 2 weeks for up to 1 year in subjects without unacceptable toxicity who achieve complete remission; and up to 2 years in subjects with partial response (PR) or stable disease (SD) with clinical benefit if they are tolerating nivolumab
- overall response rate of nivolumab in patients with EBV-positive LPDand EBV-positive NHL [ Time Frame: one year ]number of patients who respond to the protocol therapy (CR, PR, SD)
- toxicity profile of nivolumab in patients with EBV-LPD and EBVNHL [ Time Frame: 4 weeks ]number and type of AEs experienced
- duration of remission for patients who respond to nivolumab [ Time Frame: 4 weeks ]number of months patients stay in remission
- PFS of patients with EBV-LPD and EBV-NHL treated with nivolumab [ Time Frame: annually ]number of patients who do not experience progressive disease
- overall survival of patients with EBVLPD and EBV-NHL treated withnivolumab [ Time Frame: annually ]number of patients that survive 5 years or more
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258567
|Contact: Maureen E Edgerly, R.N.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Mark J Roschewski, M.D.||National Cancer Institute (NCI)|