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| ID | Type | Description | Link |
|---|---|---|---|
| R21CA132279-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Brigham and Women's Hospital | OTHER |
| Massachusetts General Hospital | OTHER |
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EBV-stimulated cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epstein-Barr Virus Specific Immunotherapy | Biological |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Restaging scans were performed every 8 weeks on treatment up to 20 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Glenn Hanna, MD | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana-Farber Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28222215 | Result | 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. |
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There are no plans to share IPD. Cumulative results will be posted and published.
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Participants enrolled from April 2009 to July 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The analysis dataset is comprised of eligible and treated participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The analysis dataset is comprised of eligible and treated participants. | Posted | Number | 90% Confidence Interval | percentage of participants | Restaging scans were performed every 8 weeks on treatment up to 20 weeks. |
|
Serious Adverse Events and Other Adverse Events were assessed throughout the treatment duration for up to 66 months. All-Cause Mortality was monitored until death or when lost-to-follow-up, for up to 92 months.
Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EBV-stimulated Cytotoxic T-lymphocyte (EBV-CTL) Immunotherapy | Eligible participants undergo a blood draw to obtain peripheral blood mononuclear cells (PBMCs) used for preparation of the immunotherapy product [estimated time 14-16 weeks]. Participants receive palliative chemotherapy for NPC as standard of care during the period required for T-cell production. Each participant receives a minimum of 2 T-cell product infusions, given 2 weeks apart. A 3rd infusion may be given 8-12 weeks later based on response, tolerability and sufficient immunotherapy product reserves.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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection w/ unk ANC conjunctiva | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
The number of evaluable participants did not meet protocol objectives (n=13 versus target n=18).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Glenn Hanna | Dana-Farber Cancer Institute | 617.632.6799 | GJHANNA@PARTNERS.ORG |
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| ID | Term |
|---|---|
| D000077274 | Nasopharyngeal Carcinoma |
| D020031 | Epstein-Barr Virus Infections |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| 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 | 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) | 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. |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| 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. | The analysis dataset is comprised of eligible and treated participants. | Posted | Median | 95% Confidence Interval | months | Restaging scans were performed every 8 weeks until PD. Follow-up duration was up to 92 months. |
|
|
|
| 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. | The analysis dataset is comprised of eligible and treated participants. | Posted | Count of Participants | Participants | Adverse events were assessed after each infusion treatment. Treatment duration was up to 66 months. |
|
|
|
| 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. | The analysis dataset is comprised of eligible and treated participants. | Posted | Median | 95% Confidence Interval | months | Participants were followed for survival per institutional practice until death or lost-to-follow-up. Follow-up duration was up to 92 months. |
|
|
|
| 8 |
| 13 |
| 0 |
| 13 |
| 13 |
| 13 |
| Otitis, external ear (non-infectious) | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
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| Ocular-other | Eye disorders | CTCAE (3.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdomen, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dental/teeth/peridontal, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Stomach, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constitutional, other | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain-other | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flu-like syndrome | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection Gr0-2 neut, sinus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection-other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Nonneuropathic lower extr muscle weak | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Back, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bone, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Joint, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Taste disturbance | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy-sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neurologic-other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Head/headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory tract hemorrhage NOS | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Throat/pharynx/larynx, pain | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary/Upper Respiratory-other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nail changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Pruritus/itching | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Skin-other | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D009303 |
| Nasopharyngeal Neoplasms |
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009302 | Nasopharyngeal Diseases |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |