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

NCT ID: NCT00834093

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2017-02-28

Brief Summary

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.

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.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Epstein-Barr Virus Specific Immunotherapy

Intervention Type: BIOLOGICAL

Interventions

Epstein-Barr Virus Specific Immunotherapy

Intervention Type: BIOLOGICAL

Other Intervention Names

Cell based vaccine

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Glenn J. Hanna

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Glenn Hanna, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Huang J, Fogg M, Wirth LJ, Daley H, Ritz J, Posner MR, Wang FC, Lorch JH. Epstein-Barr virus-specific adoptive immunotherapy for recurrent, metastatic nasopharyngeal carcinoma. Cancer. 2017 Jul 15;123(14):2642-2650. doi: 10.1002/cncr.30541. Epub 2017 Feb 21.

Reference Type: RESULT

PMID: 28222215 (View on PubMed)

Other Identifiers

R21CA132279-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

08-292

Identifier Type: -

Identifier Source: org_study_id