EBV-induced LymphomasPhase 1/2NCT00002663

Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies

A Phase 1/2 study testing Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in people with EBV-induced Lymphomas and EBV-associated Malignancies, run by Atara Biotherapeutics at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Any age
Conditions the study is for: EBV-induced Lymphomas, EBV-associated Malignancies, Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma
What is being tested?: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 1 siteUnited States
Study dates: Mar 1995to Jul 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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
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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Memorial Sloan Kettering Cancer Center
New York, New York, 10065

Other trials in United States

About this study

Official title: 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

Conditions: EBV-induced Lymphomas, EBV-associated Malignancies, Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma
Being tested: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
Keywords: stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, childhood Burkitt lymphoma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma
Medical subject headings: Hodgkin Disease, Lymphoma, T-Cell, Cutaneous, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Recurrence, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)Biological
Also called tabelecleucel (tab-cel®, ATA129), allogeneic EBV-CTLs, transplant donor-derived EBV-CTLs
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.

Study groups in NCT00002663
Study group	Role	What they receive
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. Receives: Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only)	Experimental	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. Receives: Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)
EBV+ PTLD-SOT R/R Rituximab + Chemo (EBV-CTLs Only)	Experimental	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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: From Day 1 through 251.1 months after Day 1 dose

Secondary outcomes (5)

Overall Survival (OS)
The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through 251.1 months after Day 1 dose
OS Rate at 12 Months
Percentage of participants with OS at 12 months are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through 12 months after Day 1 dose
OS Follow-up Time
The OS at follow-up time are reported. The OS is defined as the time from the first dose of tabelecleucel or EBV-CTLs to the date of death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through 251.1 months after Day 1 dose
Time to Response (TTR)
The TTR was defined as the time from the date of the first dose of tabelecleucel or EBV-CTLs to the date of a PR or CR, whichever occurred first. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR was 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 or EBV-CTLs; and a PR was 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 or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR was defined as clearance of EBV without subsequent development of EBV+ LPD; and PR was defined as at least a 10-fold decrease in EBV DNA levels.
Measured: From Day 1 through 251.1 months after Day 1 dose
Clinical Benefit Rate (CBR)
The CBR was the proportion of participants who have achieved a CR, PR or SD assessed at least 28 days after first dose date of study drug. For participants with clinically and/or radiologically evident EBV LPD or malignancies, CR as complete resolution of all clinical and radiologic evidence of lymphoma, confirmed by biopsy of affected tissues when indicated, lasting for at least 3 weeks following completion of a cycle of tabelecleucel or EBVCTLs; and a PR as a >= 50% reduction in size of all lymphomatous lesions as determined by CT or MRI scan measurements of tumor volume, maintained for at least 3 weeks following completion of a cycle of tabelecleucel or EBV-CTLs. For participants without clinically and/or radiologically evident tumors with increasing levels of EBV DNA, CR as clearance of EBV without subsequent development of EBV+ LPD; and PR as at least a 10-fold decrease in EBV DNA levels. The CBR was included specifically as clinically meaningful for solid tumor, namely LMS.
Measured: From Day 1 through 251.1 months after Day 1 dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 1995Jul 2019

First posted27 Jan 2003 (estimated)
Study startMar 1995
Primary completionJul 2019
Study completionJul 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for EBV-induced LymphomasStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00002663
Sponsor's protocol ID: 95-024
Other IDs: P30CA008748, MSKCC-95024, NCI-V95-0685
Status last verified: Jan 2023
First submitted: 1 Nov 1999
Last updated: 13 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Expanded access: Available

Publications

Prockop S, Doubrovina E, Suser S, Heller G, Barker J, Dahi P, Perales MA, Papadopoulos E, Sauter C, Castro-Malaspina H, Boulad F, Curran KJ, Giralt S, Gyurkocza B, Hsu KC, Jakubowski A, Hanash AM, Kernan NA, Kobos R, Koehne G, Landau H, Ponce D, Spitzer B, Young JW, Behr G, Dunphy M, Haque S, Teruya-Feldstein J, Arcila M, Moung C, Hsu S, Hasan A, O'Reilly RJ. Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation. J Clin Invest. 2020 Feb 3;130(2):733-747. doi: 10.1172/JCI121127.
PubMed 31689242

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruitingPhase 2
GELAD-Based Response-Adapted Treatment for Early-Stage Extranodal NK/T-Cell Lymphoma
Natural Killer/T-cell Lymphoma
RecruitingPhase 3
BRIDGE-NK: Immunotherapy Versus Chemotherapy Induction Followed by Autologous HSCT in Advanced NKTCL
Extranodal NK/T-cell Lymphoma
Not yet recruitingPhase 1
Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30)
Diffuse Large B-Cell Lymphoma (DLBCL), Hodgkin Lymphoma

All EBV-induced Lymphomas trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT00002663
Acronym / sponsor ID: 95-024
Conditions: EBV-induced Lymphomas, EBV-associated Malignancies, Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma
Keywords: stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Atara BiotherapeuticsIndustry (pharma, biotech, devices)
Collaborators: Memorial Sloan Kettering Cancer Center, National Cancer Institute (NCI)
Study start: Mar 1995 (actual)
Primary completion: Jul 2019 (actual)
Study completion: Jul 2019 (actual)
First posted: 27 Jan 2003 (estimated)
Results: Posted 13 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 10

Arm	Type	Receives
EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only)	Experimental	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.
EBV+ AID-LPD (Tab-cel Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ LMS (Tab-cel Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ NPC (Tab-cel Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ PTLD-SOT R/R Rituximab + Chemo (EBV-CTLs Only)	Experimental	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.
EBV+ Viremia (EBV-CTLs Only)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ PID-LPD (Tab-cel or EBV-CTLs)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.
EBV+ Lymphoma (Tab-cel or EBV-CTLs)	Experimental	Biological: Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)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.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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
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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)Also: tabelecleucel (tab-cel®, ATA129), allogeneic EBV-CTLs, transplant donor-derived EBV-CTLsEBV-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.	Biological	EBV+ AID-LPD (Tab-cel Only), EBV+ LMS (Tab-cel Only), EBV+ Lymphoma (Tab-cel or EBV-CTLs), EBV+ NPC (Tab-cel Only), EBV+ PID-LPD (Tab-cel or EBV-CTLs), EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only), EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only), EBV+ PTLD-SOT R/R Rituximab + Chemo (EBV-CTLs Only), EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only), EBV+ Viremia (EBV-CTLs Only)

Primary outcome

Objective Response Rate (ORR)
Time frame: From Day 1 through 251.1 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.

5 secondary outcomes

Overall Survival (OS)
Time frame: From Day 1 through 251.1 months after Day 1 dose
OS Rate at 12 Months
Time frame: From Day 1 through 12 months after Day 1 dose
OS Follow-up Time
Time frame: From Day 1 through 251.1 months after Day 1 dose
Time to Response (TTR)
Time frame: From Day 1 through 251.1 months after Day 1 dose
Clinical Benefit Rate (CBR)
Time frame: From Day 1 through 251.1 months after Day 1 dose

Results and safety

Results posted to the registry on 13 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only)	11	4
EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only)	4	2
EBV+ AID-LPD (Tab-cel Only)	2	1
EBV+ LMS (Tab-cel Only)	5	3
EBV+ NPC (Tab-cel Only)	1	0
EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only)	23	8
EBV+ PTLD-SOT R/R Rituximab + Chemo (EBV-CTLs Only)	2	1
EBV+ Viremia (EBV-CTLs Only)	6	4
EBV+PID-LPD (Tab-cel or EBV-CTLs Only)	2	0
EBV+ Lymphoma (Tab-cel or EBV-CTLs Only)	2	0

Primary outcome: Objective Response Rate (ORR)

Time frame: From Day 1 through 251.1 months after Day 1 dose. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only) n = 11	EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only) n = 4	EBV+ LMS (Tab-cel Only) n = 5	EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only) n = 23	EBV+ Viremia (EBV-CTLs Only) n = 7
Value	63.6 (30.8 to 89.1)	50.0 (6.8 to 93.2)	0 (0 to 52.2)	43.5 (23.2 to 65.5)	57.1 (18.4 to 90.1)

Population analysed: Full analysis set included all participants who received at least one dose of study treatment (tabelecleucel or EBV-CTLs). Results from arms with \<= 3 participants (as shown in the participant flow) are excluded due to the low numbers of participants; these low numbers pose a risk for participant re-identification in these rare indications of this single center study.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 through 251.1 months after Day 1 dose. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Overall Total	40 of 58 (69%)	0 of 0	32 of 58

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31689242Prockop S, Doubrovina E, Suser S, Heller G, Barker J, Dahi P, Perales MA, Papadopoulos E, Sauter C, Castro-Malaspina H, Boulad F, Curran KJ, Giralt S, Gyurkocza B, Hsu KC, Jakubowski A, Hanash AM, Kernan NA, Kobos R, Koehne G, Landau H, Ponce D, Spitzer B, Young JW, Behr G, Dunphy M, Haque S, Teruya-Feldstein J, Arcila M, Moung C, Hsu S, Hasan A, O'Reilly RJ. Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation. J Clin Invest. 2020 Feb 3;130(2):733-747. doi: 10.1172/JCI121127.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Minoti Hiremath, MD study director

Atara Biotherapeutics

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From Day 1 through 251.1 months after Day 1 dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00002663, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2023.