Clinical trial NCT00834093: A Phase II Study of Epstein-Barr Virus-Specific Immunotherapy for Nasopharyngeal Carcinoma
Official title: A Phase II Study of Epstein-Barr Virus-Specific Immunotherapy for Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: Epstein-Barr Virus
NPC
EBV
immunotherapy
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: National Cancer Institute (NCI)
First posted: 2009-02-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Best Overall Response Rate (ORR)
timeFrame: Restaging scans were performed every 8 weeks on treatment up to 20 weeks.
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: Restaging scans were performed every 8 weeks until PD. Follow-up duration was up to 92 months.
measure: Number of Participants With Grade 1-2 Fatigue Adverse Events," as Accurate and Appropriate
timeFrame: Adverse events were assessed after each infusion treatment. Treatment duration was up to 66 months.
measure: Overall Survival (OS)
timeFrame: Participants were followed for survival per institutional practice until death or lost-to-follow-up. Follow-up duration was up to 92 months.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Glenn Hanna, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.