Nasopharyngeal Carcinoma
Conditions
Keywords
Epstein-Barr Virus, NPC, EBV, immunotherapy
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.
Interventions
BIOLOGICALEpstein-Barr Virus Specific Immunotherapy
Sponsors
Brigham and Women's Hospital
Massachusetts General Hospital
National Cancer Institute (NCI)
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (ORR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | 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. |
| Number of Participants With Grade 1-2 Fatigue Adverse Events, as Accurate and Appropriate | 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. |
| Overall Survival (OS) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants enrolled from April 2009 to July 2011.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive Disease | 3 |
| Overall Study | Withdrawal by subject or MD Decision | 5 |
Baseline characteristics
| Characteristic | EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy |
|---|---|
| Age, Continuous | 49 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Best Overall Response Rate (ORR)
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.
Time frame: Restaging scans were performed every 8 weeks on treatment up to 20 weeks.
Population: The analysis dataset is comprised of eligible and treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Best Overall Response Rate (ORR) | 0.0 percentage of participants |
Secondary
Number of Participants With Grade 1-2 Fatigue Adverse Events, as Accurate and Appropriate
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.
Time frame: Adverse events were assessed after each infusion treatment. Treatment duration was up to 66 months.
Population: The analysis dataset is comprised of eligible and treated participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Number of Participants With Grade 1-2 Fatigue Adverse Events, as Accurate and Appropriate | 9 Participants |
Secondary
Overall Survival (OS)
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.
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.
Population: The analysis dataset is comprised of eligible and treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Overall Survival (OS) | 25.0 months |
Secondary
Time to Progression (TTP)
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.
Time frame: Restaging scans were performed every 8 weeks until PD. Follow-up duration was up to 92 months.
Population: The analysis dataset is comprised of eligible and treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Time to Progression (TTP) | 7.9 months |