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

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Nasopharyngeal Carcinoma

Treatments: Biological: Epstein-Barr Virus Specific Immunotherapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00834093

08-292

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

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

EBV-stimulated cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy

Experimental group

Description:

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.

Treatment:

Biological: Epstein-Barr Virus Specific Immunotherapy