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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 80
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies, Monoclonal; Nivolumab
• Last Updated: 2017-08-23

Criteria

• INCLUSION CRITERIA:

• Subjects must have histologically or cytologically confirmed EBV-positive LPD or an EBV-positive NHL confirmed by the Laboratory of Pathology, NCI.

• Cohort 1: EBV-positive B-cell LPD. Subjects may be previously untreated or relapsed from prior therapy.

1. Lymphomatoid granulomatosis (LYG), grades I-II

2. Chronic active EBV disease (CAEBV)

3. EBV-positive post-transplantation lymphoproliferative disorder (PTLD)

NOTE: PTLD after solid organ transplantation is excluded.

• Cohort 2: EBV-positive B-cell NHL subjects must have relapsed from previous treatment with an anthracycline-based regimen or be considered not eligible for treatment with an anthracycline-based regimen.

1. Lymphomatoid granulomatosis (LYG), grade III

2. EBV-positive immunodeficiency-associated diffuse large B-cell lymphoma (DLBCL)

3. 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 greater than or equal to 12 years

• Adequate performance status as follows:

• Patients greater than or equal to 16 years must have ECOG Performance Status 0-2 (Karnofsky greater than or equal to 60%)

• Pediatric patients < 16 years must have Lansky play-performance of 60-100%

• Subjects must have measurable or evaluable disease.

• Subjects must have adequate organ and bone marrow reserve (unless disease-related) as defined below:

• absolute neutrophil count - greater than or equal to 750/mcL; unless impairment is due to LPD/NHL

• platelets - greater than or equal to 50,000/mcL unless impairment is due to LPD/NHL; (transfusions not permitted)

• Hemoglobin greater than or equal to 9g/dL (transfusion permitted)

• total bilirubin - < 3.0g/dl OR < 5.0g/dl if Gilbert s syndrome or disease infiltration of the liver is present

• AST(SGOT)/ALT(SGPT) less than or equal to 3 X institutional upper limit of normal

• serum creatinine (adults) OR creatinine clearance less than or equal to 1.5 mg/dL OR greater than or equal to 40 ml/min/1.73m(2) unless lymphoma related

• serum creatinine OR creatinine clearance - serum Cr less than or equal to age-adjusted normal OR greater than or equal to 40 ml/min/1.73m2 unless lymphoma related

• A formalin fixed tissue block or at least 15 slides of tumor sample (archival or fresh) must be available for performance of correlative studies. NOTE: Patient must be willing to have a pre-treatment tumor biopsy if adequate archival tissue is not available.

• The toxicity profile of nivolumab in patients with disease involvement of the central nervous system (CNS) is unknown. For this reason, we will introduce early stopping rules.

• The effects of nivolumab on the developing human fetus are unknown. For this reason, the following measures apply:

• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 48 hours prior to the start of the first dose of nivolumab.

• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.

• Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.

• WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral ophorectomy), and who is not postmenopausal. Post menopause is defined as:

1. Amenorrhea greater than or equal to 12 consecutive months without another cause, and a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL or

2. Women with irregular menstrual periods and a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL or NOTE: FSH level testing is not required for women greater than or equal to 62 years old with amenorrhea of greater than or equal to 1 year

3. Women on hormone replacement therapy (HRT)

• Pregnant women are excluded from this study because nivolumab is an IgG monoclonal antibody with the potential for teratogenic or abortifacient effects.

• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab.

• Ability of subject or Legally Authorized Representative (LAR) to understand and sign the written informed consent document.

EXCLUSION CRITERIA:

• 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 premalignant 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 greater than or equal to 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.