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NonHodgkin LymphomaPhase 1PREVALENCT02973113

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

A Phase 1 study testing EBVST Cells and Nivolumab in people with NonHodgkin Lymphoma and Lymphoproliferative Disorders, run by Baylor College of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
EBVST Cells and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesUnited States
Study dates
16 Feb 2016to 11 Jul 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • PROCUREMENT Inclusion
  • 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
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  • 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.
  • TREATMENT Inclusion
  • 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
  • Patients with life expectancy >/= 6 weeks.
  • Patients with bilirubin less than or equal to 3x upper limit of normal
  • AST less than or equal to 5x upper limit of normal
  • Hgb more than 8.0 (may be a transfused value).
  • Patients with a creatinine less than or equal to 2x upper limit of normal for age
  • Pulse oximetry of more than 90% on room air
  • Patients should have been off other investigational therapy for 4 weeks prior to entry in this study.
  • Patients with a Karnofsky/Lansky score of >/= 60
  • Recovered from acute toxic effects of prior chemotherapy at least one week before entering the study.
  • Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
  • Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given a copy of informed consent.

Who cannot join

  • PROCUREMENT Exclusion
  • Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)
  • History of solid organ transplant
  • TREATMENT Exclusion
  • Pregnant or lactating due to unknown effects of this therapy on a fetus or lactation
  • Severe active intercurrent infection.
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • Texas Children's Hospital

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study Combining Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS) in Relapsed/Refractory EBV Positive Lymphoma Patients (PREVALE)

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.

Read more

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.

Read the detailed description

The investigators will draw blood from the subject to make EBV-specific cytotoxic T-lymphocytes (EBVSTs) in the lab. Investigators will make the cells by first growing a special type of cells called dendritic cells (DCs) or monocytes to stimulate the T cells. Then they will add specially produced mixtures of proteins that included the LMP, EBNA1, and BARF proteins. These are used to stimulate T cells. As the T cells grow, investigators add some of the subject's cells expressing these proteins to stimulate them. They also add a cell called K562 that has had new genes put inside it so it expresses proteins that stimulate the immune system to encourage the T cells to grow. This stimulation trains the EBVSTs to kill cells with EBV proteins on their surface. These cells will be grown and frozen.

The cells grown in the lab will be thawed and injected into the subject's vein over 2-10 minutes. Initially, one dose of the drug nivolumab is given one day before the EBVST cells are infused (on day 0) and then every 2 weeks for a total of four doses of nivolumab. Subjects will receive two infusions of the EBVST cells. The first infusion will be given on Day 1 and a second infusion of T cells on Day 15.

If eligible, subjects may receive up to three additional doses of the T cells 6-12 weeks apart and each additional T cell infusion would be preceded by one dose of nivolumab a day prior.

Subjects will have medical and blood tests at predetermined time points. Investigators will follow subjects closely after treatment for any side effects for at least for 1 year after the subject's last infusion.

Being tested
EBVST Cells, Nivolumab
Keywords
Nivolumab, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorders, EBV-specific T Cells
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoproliferative Disorders, Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EBVST CellsBiological

    Also called EBV-specific T Cells

    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.

  • NivolumabBiological

    Also called Opdivo

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

Study groups in NCT02973113
Study groupRoleWhat they receive
EBVST Cells + NivolumabExperimentalPD1 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
Receives: Biological: EBVST Cells; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 months

Secondary outcomes (1)

  1. Duration of Overall Response

    The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.

    The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2016 (estimated)
  2. Study start16 Feb 2016
  3. Primary completion5 Sep 2019
  4. Study completion11 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02973113
Sponsor's protocol ID
H-39090 PREVALE
Other IDs
PREVALE
Acronym
PREVALE
Status last verified
Jul 2021
First submitted
22 Nov 2016
Last updated
21 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39908567

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EBVST Cells and Nivolumab in people with NonHodgkin Lymphoma and Lymphoproliferative Disorders, run by Baylor College of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Dose-Limiting Toxicities (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02973113, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2021.

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