Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies
An Evaluation of the Toxicity and Therapeutic Effects of Epstein-Barr Virus-Immune T-Lymphocytes Derived From a Normal HLA-Compatible or Haplotype-Matched Donor in the Treatment of EBV-Associated Lymphoproliferative Diseases or Malignancies and Patients With Detectable Circulating Levels of EBV DNA Who Are at High Risk for EBV-Associated Lymphoproliferative Diseases
The purpose of this phase I/II trial is to study the side effects and best dose of biological therapy to treat patients at high-risk or with Epstein-Barr virus-associated lymphoma or lymphoproliferative disease.
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)
58 participants
Study completion date
July 2019
Actual (reported)
Listed locations
1 countries · 1 sites
Trial Relationships
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Related Scientific Literature
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Study Timeline
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
stage I adult Hodgkin lymphomastage II adult Hodgkin lymphomastage III adult Hodgkin lymphomastage IV adult Hodgkin lymphomarecurrent adult Hodgkin lymphomastage I cutaneous T-cell non-Hodgkin lymphomastage II cutaneous T-cell non-Hodgkin lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomachildhood Burkitt lymphomastage I childhood lymphoblastic lymphomastage II childhood lymphoblastic lymphomastage III childhood lymphoblastic lymphomastage IV childhood lymphoblastic lymphomarecurrent childhood lymphoblastic lymphomachildhood diffuse large cell lymphomachildhood immunoblastic large cell lymphomastage II childhood Hodgkin lymphomastage I childhood Hodgkin lymphomastage III childhood Hodgkin lymphomastage IV childhood Hodgkin lymphomarecurrent/refractory childhood Hodgkin lymphomastage I grade 1 follicular lymphomastage I grade 2 follicular lymphomastage I grade 3 follicular lymphomastage I adult diffuse small cleaved cell lymphomastage I adult diffuse mixed cell lymphomastage I adult diffuse large cell lymphomastage I adult immunoblastic large cell lymphomastage I adult lymphoblastic lymphomastage I adult Burkitt lymphomaT-cell large granular lymphocyte leukemiastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III adult diffuse small cleaved cell lymphomastage III adult diffuse mixed cell lymphomastage III adult diffuse large cell lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic lymphomastage III adult Burkitt lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse large cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV adult Burkitt lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse large cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult Burkitt lymphomastage I adult T-cell leukemia/lymphomastage II adult T-cell leukemia/lymphomastage III adult T-cell leukemia/lymphomastage IV adult T-cell leukemia/lymphomarecurrent adult T-cell leukemia/lymphomaAIDS-related peripheral/systemic lymphomaHIV-associated Hodgkin lymphomastage I childhood small noncleaved cell lymphomastage I childhood large cell lymphomastage II childhood small noncleaved cell lymphomastage II childhood large cell lymphomastage III childhood small noncleaved cell lymphomastage III childhood large cell lymphomastage IV childhood small noncleaved cell lymphomastage IV childhood large cell lymphomarecurrent childhood small noncleaved cell lymphomarecurrent childhood large cell lymphomastage I mantle cell lymphomacontiguous stage II grade 1 follicular lymphomacontiguous stage II grade 2 follicular lymphomacontiguous stage II grade 3 follicular lymphomacontiguous stage II adult diffuse small cleaved cell lymphomacontiguous stage II mantle cell lymphomacontiguous stage II adult diffuse mixed cell lymphomacontiguous stage II adult immunoblastic large cell lymphomacontiguous stage II adult diffuse large cell lymphomacontiguous stage II adult Burkitt lymphomacontiguous stage II adult lymphoblastic lymphomanoncontiguous stage II grade 1 follicular lymphomanoncontiguous stage II grade 2 follicular lymphomanoncontiguous stage II grade 3 follicular lymphomanoncontiguous stage II adult diffuse small cleaved cell lymphomanoncontiguous stage II mantle cell lymphomanoncontiguous stage II adult diffuse mixed cell lymphomanoncontiguous stage II adult immunoblastic large cell lymphomanoncontiguous stage II adult diffuse large cell lymphomanoncontiguous stage II adult Burkitt lymphomanoncontiguous stage II adult lymphoblastic lymphomastage III mantle cell lymphomastage IV mantle cell lymphomarecurrent mantle cell lymphomastage I mycosis fungoides/Sezary syndromestage II mycosis fungoides/Sezary syndromestage III mycosis fungoides/Sezary syndromestage IV mycosis fungoides/Sezary syndromerecurrent mycosis fungoides/Sezary syndromecontiguous stage II small lymphocytic lymphomacontiguous stage II marginal zone lymphomanoncontiguous stage II small lymphocytic lymphomanoncontiguous stage II marginal zone lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomastage I marginal zone lymphomastage I small lymphocytic lymphomastage III small lymphocytic lymphomastage III marginal zone lymphomastage IV small lymphocytic lymphomastage IV marginal zone lymphomaunspecified adult solid tumor, protocol specificunspecified childhood solid tumor, protocol specific
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR)
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 251.1 months after Day 1 dose
Secondary Outcomes (5)
Overall Survival (OS)
From Day 1 through 251.1 months after Day 1 dose
Study Arms (10)
EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only)
EXPERIMENTAL
Patients with Epstein-Barr virus positive (EBV+) posttransplant lymphoproliferative disorders (PTLD) following hematopoietic cell transplant (HCT) who were relapse/refractory (R/R) to rituximab will receive IV infusion of tabelecleucel (tab-cel) at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Patients with EBV+ PTLD following solid organ transplant (SOT) who were R/R to rituximab and chemotherapy will receive IV infusion of tabelecleucel at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Interventions
Epstein-Barr virus-specific cytotoxic T lymphocytes (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.
Also known as: tabelecleucel (tab-cel®, ATA129), allogeneic EBV-CTLs, transplant donor-derived EBV-CTLs
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 OR
Severely immunocompromised patients who develop blood levels of EBV DNA exceeding 500 copies/ml DNA, and are therefore at high risk for developing an EBV LPD
Hodgkin DiseaseLymphoma, T-Cell, CutaneousBurkitt LymphomaLymphoma, Large B-Cell, DiffuseRecurrenceLymphoma, FollicularLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Large Granular LymphocyticPrecursor T-Cell Lymphoblastic Leukemia-LymphomaDendritic Cell Sarcoma, InterdigitatingLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLymphoma, B-Cell, Marginal Zone
Limitations and Caveats
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 95-024 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.
58 participants (actual enrollment reported by the registry).
Study Design
Study Type
interventional
Phase
phase 1 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
November 1, 1999
First Posted
January 27, 2003
Study Start
March 1995
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 251.1 months after Day 1 dose
Time to Response (TTR)
From Day 1 through 251.1 months after Day 1 dose
Clinical Benefit Rate (CBR)
From Day 1 through 251.1 months after Day 1 dose
EBV+ AID-LPD (Tab-cel Only)
EXPERIMENTAL
Patients with EBV+ acquired immunodeficiency (AID) lymphoproliferative disorder (LPD) will receive IV infusion of tabelecleucel at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ LMS (Tab-cel Only)
EXPERIMENTAL
Patients with EBV+ leiomyosarcoma (LMS) will receive IV infusion of tabelecleucel at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ NPC (Tab-cel Only)
EXPERIMENTAL
Patients with EBV+ nasopharyngeal carcinoma (NPC) will receive IV infusion of tabelecleucel at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only)
EXPERIMENTAL
Patients with EBV+ following PTLD HCT who were R/R to rituximab or rituximab naive will receive IV infusion of transplant donor-derived EBV-cytotoxic T lymphocytes (CTLs) at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Patients with EBV+ PTLD following SOT who were R/R to rituximab and chemotherapy will receive IV infusion of transplant donor-derived EBV-CTLs at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ Viremia (EBV-CTLs Only)
EXPERIMENTAL
Patients with EBV+ viremia will receive IV infusion of transplant donor-derived EBV-CTLs at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ PID-LPD (Tab-cel or EBV-CTLs)
EXPERIMENTAL
Patients with EBV+ primary immunodeficiency (PID) LPD will receive IV infusion of tabelecleucel or transplant donor-derived EBV- CTLs at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ Lymphoma (Tab-cel or EBV-CTLs)
EXPERIMENTAL
Patients with EBV+ lymphoma will receive IV infusion of tabelecleucel or transplant donor-derived EBV-CTLs at 1-5 × 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: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
It is expected that five types of patients afflicted with EBV-associated lymphomas or lymphoproliferative diseases will be referred and will consent to participate in this trial. These are:
Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic marrow transplant.
Patients developing or at risk for 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 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.
You may not qualify if:
The following patients will be excluded from this study:
Moribund patients who, by virtue of heart, kidney, liver, lung, or neurologic dysfunction not related to lymphoma, are unlikely to survive the 6-8 weeks required for in vitro generation and expansion of the EBV-specific T cells to be used for therapy and the subsequent 3 weeks required to achieve an initial assessment of the effects of infusions of EBV-specific T cells.
Pregnancy does not constitute a contraindication to infusions of EBV-specific T cells.
Contact the study team to confirm eligibility.
NIHcollaborator
Leukemia, Lymphocytic, Chronic, B-Cell
Condition Hierarchy (Ancestors)
LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, T-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, LymphoidLeukemiaHematologic DiseasesLeukemia, T-CellHistiocytic Disorders, MalignantHistiocytosisLeukemia, B-CellChronic Disease
Primary Completion
July 2019
Actual (reported)
Study Completion
July 2019
Actual (reported)
Last Updated
February 13, 2023
Results First Posted
February 13, 2023
Record last verified: 2023-01
Source record
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Source: ClinicalTrials.gov.
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