- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01498484
Therapeutic Effects of Epstein-Barr Virus Immune T-Lymphocytes Derived From a Normal HLA-Compatible Or Partially-Matched Third-Party Donor in the Treatment of EBV Lymphoproliferative Disorders and EBV-Associated Malignancies
A Phase II Study of the Therapeutic Effects Of Epstein-Barr Virus Immune T-Lymphocytes Derived From a Normal HLA-Compatible Or Partially-Matched Third-Party Donor in the Treatment of EBV Lymphoproliferative Disorders and EBV-Associated Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Expanded Access
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma or other EBV-associated malignancy.
OR
- Evaluable disease as demonstrated by clinical and/or radiologic studies with current or prior elevated blood levels of EBV DNA exceeding 500 copies/ml by quantitative real time polymerase chain reaction (PCR).
OR
- Persistent or recurrent elevations in levels of EBV DNA exceeding 500 copies/ml in patients previously treated for EBV-LPD with chemotherapy and/or rituximab who do not yet have clinically or radiologically evaluable disease but are at high risk of disease recurrence.
- EBV-specific T cells are available for adoptive immune cell therapy from a consenting third party donor. The third party EBV-CTLs to be administered will be selected on the basis of two criteria: 1) that they are matched for at least 2 HLA antigens and 2) that they are restricted by an allele shared with the EBV+ malignancy (if known), or with the donor in HSCT recipients, or patient in organ transplant or immunodeficient patients
- KPS or Lansky score ≥ 20.
- A life expectancy of at least 6 weeks.
Adequate bone marrow, heart, lung, liver and kidney function at the time of treatment with EBV-specificT cells is initiated, including:
- Absolute neutrophil count (ANC) ≥ 1,000/µL, with or without GCSF support
- Platelets ≥ 20,000/µL
- Creatinine ≤ 2.0mg/dl
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3.0x and total bilirubin < 2.5x the institutional upper limit of normal (ULN)
- Stable blood pressure and circulation not requiring pressor support
- Adequate cardiac function as demonstrated by EKG and/or echocardiographic evidence (may be performed within 30 days prior to treatment)
- However, abnormalities of specific organs will not be considered grounds for exclusion if they are the result of the EBV+ malignancy or its treatment (e.g. a renal allograft recipient with an EBV LPD may be on dialysis because the allograft was rejected when the immune suppression was stopped as a first approach to treatment of the EBV LPD). At the discretion of the investigator, patients with elevated but stable creatinine will not be precluded from treatment on study.
- There is no age restriction to eligibility for this protocol.
It is expected that five types of patients afflicted with EBV-associated lymphomas, lymphoproliferative diseases or malignancies will be referred and will consent to participate in this trial. These are:
- Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic hematopoietic progenitor stem cell transplant (HSCT) (ie, marrow, PBSC, or umbilical cord blood).
- Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant.
- Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by HIV.
- Patients who develop EBV lymphomas or lymphoproliferative diseases or other EBV-associated malignancy as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy.
- Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and Non-Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma.
Exclusion Criteria:
The following patients will be excluded from this study:
- Patients with active (grade 2-4) acute graft vs. host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring high doses of glucocorticosteroid (>0.5 mg/kg/day prednisone or its equivalent) as treatment
- Patients who are pregnant
- Patients with severe comorbidities, not related to their EBV-associated malignancy, that would be expected to preclude their survival for the 6 weeks required to assess response of T cell therapy
- Patients eligible for MSK protocol #16-803 (EBV-CTL-201)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HCT EBV+ PTLD R/R Rituximab
Patients with Epstein-Barr virus positive (EBV+) posttransplant lymphoproliferative disorders (PTLD) hematopoietic cell transplant (HCT) who were relapse/refractory (R/R) to rituximab will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: SOT EBV+ PTLD R/R Rituximab
Patients with EBV+PTLD solid organ transplant (SOT) who were R/R to rituximab or R/R to rituximab and chemotherapy will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After 3 week observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ AID-LPD
Patients with EBV+ acquired immunodeficiency (AID) lymphoproliferative disorder (LPD) will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ PID-LPD
Patients with EBV+ primary immunodeficiency (PID) LPD will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ Viremia
Patients with EBV+ viremia will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ Leiomyosarcoma
Patients with EBV+ leiomyosarcoma (LMS) will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ Lymphoma
Patients with EBV+ lymphoma will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ NPC
Patients with EBV+ nasopharyngeal carcinoma (NPC) will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
Experimental: EBV+ Other Solid Tumor
Patients with EBV+ other solid tumors will receive IV infusion of tabelecleucel 2 × 10^6 T-cells/kg on Days 1, 8, and 15 and will be observed for 3 weeks.
After the observation period, additional courses (2 courses) may have been provided in the absence of disease progression or unacceptable toxicity.
|
EBV-CTLs are cytotoxic T lymphocytes that specifically kill cells presenting EBV protein antigens including EBV-transformed B lymphocytes responsible for EBV-associated lymphomas and lymphoproliferative disorders.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: From Day 1 through 65.3 months after Day 1 dose
|
The ORR is defined as percentage of participants with best overall response of complete remission/response (CR) or partial remission/response (PR) based on investigator's assessment.
For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR is complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel; and PR is a 50 % or greater reduction in the size of all lymphomatous lesions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel.
For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR is clearance of EBV without subsequent development of EBV+ LPD; and PR is at least a 10-fold decrease in EBV DNA levels.
|
From Day 1 through 65.3 months after Day 1 dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: From Day 1 through 65.3 months after Day 1 dose
|
The OS is defined as the time from the first dose of tabelecleucel to the date of death due to any cause.
The OS was estimated using Kaplan-Meier method.
Participants who were lost to follow-up or still alive were censored on the last known-to-be-alive date.
|
From Day 1 through 65.3 months after Day 1 dose
|
OS Rate at 12 Months
Time Frame: From Day 1 through 12 months after Day 1 dose
|
Percentage of participants with OS at 12 months are reported.
The OS is defined as the time from the first dose of tabelecleucel to the date of death due to any cause.
The OS was estimated using Kaplan-Meier method.
Participants who were lost to follow-up or still alive were censored on the last known-to-be-alive date.
|
From Day 1 through 12 months after Day 1 dose
|
OS Follow-up Time
Time Frame: From Day 1 through 65.3 months after Day 1 dose
|
The OS follow-up time are reported.
The OS is defined as the time from the first dose of tabelecleucel to the date of death due to any cause.
The OS was estimated using Kaplan-Meier method.
Participants who were lost to follow-up or still alive were censored on the last known-to-be-alive date.
|
From Day 1 through 65.3 months after Day 1 dose
|
Time to Response (TTR)
Time Frame: From Day 1 through 65.3 months after Day 1 dose
|
The TTR is defined as the time from the date of the first dose of tabelecleucel to the date of a PR or CR, whichever occurred first.
For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR is defined as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of the affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel; and a PR is defined as a 50 % or greater reduction in the size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, which was maintained for at least 3 weeks following completion of a cycle of tabelecleucel.
For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR is defined as clearance of EBV without subsequent development of EBV+ LPD; and PR is defined as at least a 10-fold decrease in EBV DNA levels.
|
From Day 1 through 65.3 months after Day 1 dose
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphatic Diseases
- Immunoproliferative Disorders
- Systemic Inflammatory Response Syndrome
- Inflammation
- DNA Virus Infections
- Sepsis
- Tumor Virus Infections
- Herpesviridae Infections
- Neoplasms
- Lymphoma
- Viremia
- Epstein-Barr Virus Infections
- Lymphoproliferative Disorders
Other Study ID Numbers
- 11-130
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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