A Phase II Study of Epstein-Barr Virus-Specific Immunotherapy for Nasopharyngeal Carcinoma

June 27, 2023 updated by: Glenn J. Hanna, Dana-Farber Cancer Institute
The purpose of this research study is to determine how effective and how safe it is to give an Epstein-Barr Virus (EBV) immunotherapy product to participants with nasopharyngeal carcinoma (NPC) associated with EBV that has come back or spread to other parts of the participant's body. This is phase II study with the aim of establishing a baseline of efficacy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study follows a pilot study optimizing and refining the manufacturing process, streamlining logistics (eg infusion protocol, enrolling out-of-town patients), increasing the cell dose, defining optimal patient eligibility, and improving monitoring for patients. Eligible participants will undergo a blood draw to obtain peripheral blood mononuclear cells (PBMCs) used for preparation of the immunotherapy product [estimated time 14-16 weeks]. Participants' PBMCs will be isolated by density centrifugation from peripheral blood and then infected with EBV to generate EBV-transformed B-lymphoblastoid cell lines (LCLs). LCLs will be irradiated and then used to stimulate autologous T cells, yielding an EBV-specific, autologous T cell product.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically proven NPC of an WHO grade, associated with EBV infection documented by the presence of EBER expression by in situ hybridization in the tumor. Positive EBER staining from another institution must be confirmed by pathology review at Brigham and Women's Hospital. Other confirmation of EBV-associated disease is acceptable, such as EBV DNA in situ hybridization, if EBER analysis is not adequate
  • Incurable NPC
  • Recovery from toxicity from any prior NPC therapy to grade 1 or better
  • 18 years of age or older
  • Evaluable or measurable disease, according to modified RECIST
  • ECOG Performance Status of 0 or 1
  • Adequate bone marrow, liver and renal function as outlined in protocol

Exclusion Criteria:

  • Radiotherapy for primary NPC within 8 weeks of enrollment, or radiotherapy for any other reason within 6 weeks
  • Chemotherapy for NPC within 2 weeks of enrollment
  • Other cancer in the past 5 years, except for carcinoma in situ of the cervix or bladder, or non-melanomatous skin cancer
  • Uncontrolled central nervous system metastases
  • Active hepatitis, known HIV, or other condition that requires immunosuppressive therapy, including current use of high dose systemic corticosteroids
  • Autoimmune disease, such as systemic lupus erythematosis or rheumatoid arthritis, that is active and requires current immunosuppressive therapy
  • Active uncontrolled serious infection
  • Women of child-bearing potential who have a positive pregnancy test or are breast-feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EBV-stimulated cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy
Eligible participants underwent a blood draw to obtain peripheral blood mononuclear cells (PBMCs) used for preparation of the immunotherapy product [estimated preparation time 14-16 weeks]. Participants received palliative chemotherapy for NPC as standard of care during the period required for T-cell production. Participants who achieved a partial response or better while receiving palliative chemotherapy continued to receive chemotherapy for 3 to 6 cycles and were only eligible for immunotherapy when progressive disease (PD) was confirmed. Each participant received a minimum of 2 EBV-CTL infusions, given 2 weeks apart, at doses of 1x108 cells/m2. A 3rd infusion was offered to participants 8-12 weeks after the 2nd infusion based on response, tolerability and sufficient immunotherapy product reserves.
Biological: Epstein-Barr Virus Specific Immunotherapy
Other Names:
  • Cell based vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response Rate (ORR)
Time Frame: Restaging scans were performed every 8 weeks on treatment up to 20 weeks.
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Restaging scans were performed every 8 weeks on treatment up to 20 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP)
Time Frame: Restaging scans were performed every 8 weeks until PD. Follow-up duration was up to 92 months.
TTP estimated using the Kaplan-Meier method is defined as the duration of time from registration to documented first observation of progressive disease (PD), or censored at date last known progression-free. Based on RECIST 1.1, radiographic PD is defined as at least a 20% increase in the sum of the longest diameter (LD) for all target lesions (up to 10), taking as reference the smallest sum LD since beginning treatment or the appearance of one or more new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing lesions.
Restaging scans were performed every 8 weeks until PD. Follow-up duration was up to 92 months.
Number of Participants With Grade 1-2 Fatigue Adverse Events," as Accurate and Appropriate
Time Frame: Adverse events were assessed after each infusion treatment. Treatment duration was up to 66 months.
All grade 1-2 fatigue adverse events (AE) with any treatment attribution as reported on case report forms were counted. The number of participants experiencing at least one grade 1-2 fatigue AE during the time of observation.
Adverse events were assessed after each infusion treatment. Treatment duration was up to 66 months.
Overall Survival (OS)
Time Frame: Participants were followed for survival per institutional practice until death or lost-to-follow-up. Follow-up duration was up to 92 months.
OS estimated using the Kaplan-Meier (KM) method is defined as the time from registration to death, or censored at the date last known alive.
Participants were followed for survival per institutional practice until death or lost-to-follow-up. Follow-up duration was up to 92 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)
Massachusetts General Hospital
Brigham and Women's Hospital

Investigators

  • Principal Investigator: Glenn Hanna, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2009

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

February 2, 2009

First Submitted That Met QC Criteria

February 2, 2009

First Posted (Estimated)

February 3, 2009

Study Record Updates

Last Update Posted (Actual)

June 28, 2023

Last Update Submitted That Met QC Criteria

June 27, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-292
  • R21CA132279-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There are no plans to share IPD. Cumulative results will be posted and published.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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