Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS), Relapsed/Refractory EBV Positive Lymphoma (PREVALE)

NCT02973113 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: H-39090 PREVALEPREVALE
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

Subjects have a type of a lymph node cancer called Non-Hodgkin's Lymphoma (NHL) or lymphoproliferative disease (LPD), which affects their immunity, blood production, and can involve multiple other organs in the body. Their disease has come back or has not gone away after treatment. The experimental treatment plan consists of an antibody therapy called "Nivolumab" that helps the subjects' T-cells control the tumor, and special immune system cells called EBV-specific cytotoxic T lymphocytes, also a new therapy whose side effects are well studied. Some patients with NHL or LPD are infected with the virus that causes infectious mononucleosis (called Epstein-Barr virus, or EBV) before or at the time of their diagnosis. The cancer cells that are infected by EBV are able to hide from the body's immune system and escape destruction. Investigators want to see if special white blood cells, called T cells, that have been trained to kill cells infected by EBV can survive in the blood and affect the tumor. Investigators have used this sort of therapy to treat a different type of cancer that occurs after bone marrow or solid organ transplant called post-transplant lymphoma with good success. These cells are called EBV-specific cytotoxic T-lymphocytes (EBVSTs), and are effective in treating these diseases. These EBVSTs are experimental and not yet approved by the Food and Drug Administration (FDA). Sometimes it is not possible to grow these cells; or they may not last very long in the body after being given into the vein thereby having only limited time to fight the tumor. With this study, investigators aim to increase the duration of time that the T cells can last in the body and can effectively fight the cancer by using nivolumab. Nivolumab is FDA approved for treatment of other kinds of cancer like lung cancer and a skin cancer called Melanoma. The purpose of this study is to find out if EBVST cells in combination with nivolumab are safe, to learn what the side effects are, and to see whether this therapy may help patients with EBV related lymphoma or LPD.

Conditions

NonHodgkin Lymphoma; Lymphoproliferative Disorders; EBV Related Lymphoma; EBV-Related PTLD; Hodgkin Lymphoma; EBV Related Non-Hodgkin's Lymphoma; EBV Related Hodgkin's Lymphoma

Keywords

Nivolumab; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Lymphoproliferative Disorders; EBV-specific T Cells

Outcome Measures

Primary Outcomes (1)

• Number of Dose-Limiting Toxicities

  For the purpose of this study, dose limiting toxicity will be defined as any of the below listed items considered to be primarily related to the EBVST infusion or Nivolumab: * CTCAE grade 3-4 diarrhea needing steroids for more than 1 week or needing hospitalization for more than 1 week, * Pancreatitis of any grade needing hospitalization, * Pneumonitis needing hospitalization for more than a week or needing home oxygen despite appropriate treatment for 1 week. * Hepatitis grade 3 or more not resolving in 2 weeks after discontinuation of therapy, * Stomatitis/mucositis needing TPN. * Musculoskeletal symptoms affecting activities of daily living for more than 2 weeks after discontinuation of therapy.

  2 months

Secondary Outcomes (1)

• Duration of Overall Response

  Up to 1 year

Study Arms (1)

EBVST Cells + Nivolumab

EXPERIMENTAL

PD1 inhibitor - nivolumab 3 mg/kg (max dose: 240 mg) Q 2 weeks for total 4 doses and repeat a day prior to each EBVST infusion. EBVST- 1 x 10\^8/m2 at days +1 and +15. PD1 inhibitor - nivolumab 3 mg/kg (max dose: 240 mg) Q 2 weeks for total 4 doses and repeat a day prior to each EBVST infusion. Can receive up to 3 additional infusions of EBVSTs with a single dose of nivolumab at 6-12 week intervals starting at least 6 weeks after the second infusion if stable disease or a partial response at Week 8 evaluation

Biological: EBVST Cells; Biological: Nivolumab

Interventions

EBVST Cells BIOLOGICAL

EBVST cells in an expected volume of 10-20cc will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.

Also known as: EBV-specific T Cells

EBVST Cells + Nivolumab

Nivolumab BIOLOGICAL

Nivolumab 3mg/kg (max dose: 240 mg) will be administered as an intravenous infusion over 60 minutes.

Also known as: Opdivo

EBVST Cells + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Any patient, regardless of age\* or sex, with measurable EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype)\^ or EBV (associated)- T/NK- or B cell lymphoproliferative disease
• \* The first 3 patients enrolled will be adults. Patients \<18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or Nivolumab.
• \^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study.
• EBV positive tumor (can be pending)
• Weighs at least 12kg
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given a copy of informed consent.
• Life expectancy of greater than 6 weeks.
• \- Any patient, regardless of age\* or sex, with measurable EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype)\^ or EBV (associated)-T/NK- or B cell lymphoproliferative disease
• \* The first 3 patients enrolled will be adults. Patients \<18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or Nivolumab.
• \^ Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study.
• And
• Hodgkin's lymphoma patients in second relapse or first relapse and refractory to at least two lines of salvage chemotherapy including Brentuximab Vedotin or primary refractory disease after at least two lines therapy or
• Non- Hodgkin's lymphoma patients in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse or
• T/NK- or B lymphoproliferative disease in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse
• EBV positive tumor

You may not qualify if:

• Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)
• History of solid organ transplant
• Pregnant or lactating due to unknown effects of this therapy on a fetus or lactation
• Severe active intercurrent infection.
• Current use of systemic corticosteroids \>0.5 mg/kg/day
• Currently receiving any investigational agents or radiotherapy within 4 weeks prior to entering the study.
• Patients with central nervous system involvement.
• History of allergic reactions attributed to nivolumab or any other checkpoint inhibitors.
• Uncontrolled autoimmune disease needing systemic steroids or steroid sparing agents except for hypothyroidism or type I diabetes.
• History of solid organ transplant
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Lipase more than 70U/ml

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Sarathkumara YD, Van Bibber NW, Liu Z, Heslop HE, Rouce RH, Coghill AE, Rooney CM, Proietti C, Doolan DL. Differential antibody response to EBV proteome following EBVST immunotherapy in EBV-associated lymphomas. Blood Adv. 2025 Apr 8;9(7):1658-1669. doi: 10.1182/bloodadvances.2024014937.

  PMID: 39908567 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Hodgkin Disease

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma; 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

• Ravi Pingali, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director CAGT

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: February 16, 2016
• Primary Completion: September 5, 2019
• Study Completion: July 11, 2020
• Last Updated: July 21, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)