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
This is a Phase II trial to evaluate the efficacy and safety of human leukocyte antigen (HLA) partially-matched third-party allogeneic Epstein-Barr virus cytotoxic T lymphocytes (EBV-CTLs) for the treatment of EBV-induced lymphomas and EBV-associated malignancies.
Registry Overview
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
Recruitment status
completed
Actual enrollment (reported)
87 participants
Study completion date
July 2019
Actual (reported)
Listed locations
1 countries · 1 sites
Trial Relationships
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Study Timeline
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
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 Outcomes (4)
Overall Survival (OS)
From Day 1 through 65.3 months after Day 1 dose
Study Arms (9)
HCT EBV+ PTLD R/R Rituximab
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
SOT EBV+ PTLD R/R Rituximab
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
Interventions
EBV-specific T cells (EBV-CTLs)Biological
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.
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
You may qualify if:
Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma or other EBV-associated malignancy.
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).
In this investigator-led study, scans were only collected as clinically indicated in lieu of a defined schedule; therefore, disease assessment endpoints (duration of response, durable response rate, progression-free survival, time to progression) may not be reliable, hence not reported. Study 11-130 was designed for patient treatment and conducted mostly as investigator-sponsored, single-center until Atara assumed responsibility, then relevant data was transferred from the investigator to Atara.
87 participants (actual enrollment reported by the registry).
Study Design
Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes
Study Record Dates
First Submitted
December 21, 2011
First Posted
December 23, 2011
Study Start
December 2011
Actual (reported)
OS Rate at 12 Months
From Day 1 through 12 months after Day 1 dose
OS Follow-up Time
From Day 1 through 65.3 months after Day 1 dose
Time to Response (TTR)
From Day 1 through 65.3 months after Day 1 dose
EBV+ AID-LPD
EXPERIMENTAL
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
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ PID-LPD
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ Viremia
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ Leiomyosarcoma
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ Lymphoma
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ NPC
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
EBV+ Other Solid Tumor
EXPERIMENTAL
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.
Biological: EBV-specific T cells (EBV-CTLs)
SOT EBV+ PTLD R/R Rituximab
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
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)
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:
+5 more criteria
You may not qualify if:
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)
Contact the study team to confirm eligibility.
Primary Completion
July 2019
Actual (reported)
Study Completion
July 2019
Actual (reported)
Last Updated
October 21, 2022
Results First Posted
October 21, 2022
Record last verified: 2022-09
Source record
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Source: ClinicalTrials.gov.
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