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

NCT ID: NCT00002663

Last Updated: 2023-02-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-03-31

Study Completion Date

2019-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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EBV-induced Lymphomas EBV-associated Malignancies Transplant Patients With EBV Viremia at High Risk of Developing a Recurrent EBV Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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EBV+ PTLD-HCT R/R Rituximab (Tab-cel Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ PTLD-SOT R/R Rituximab + Chemo (Tab-cel Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ AID-LPD (Tab-cel Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ LMS (Tab-cel Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ NPC (Tab-cel Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ PTLD-HCT R/R Rituximab (EBV-CTLs Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ PTLD-SOT R/R Rituximab + Chemo (EBV-CTLs Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ Viremia (EBV-CTLs Only)

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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ PID-LPD (Tab-cel or 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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

EBV+ Lymphoma (Tab-cel or 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.

Group Type EXPERIMENTAL

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)

Intervention Type 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.

Interventions

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Epstein-Barr virus-specific cytotoxic T lymphocytes (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.

Intervention Type BIOLOGICAL

Other Intervention Names

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tabelecleucel (tab-cel®, ATA129), allogeneic EBV-CTLs transplant donor-derived EBV-CTLs

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic marrow transplant.
2. Patients developing or at risk for EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant.
3. Patients with AIDS developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by HIV.
4. 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.
5. 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:

* 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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Atara Biotherapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Minoti Hiremath, MD

Role: STUDY_DIRECTOR

Atara Biotherapeutics

Locations

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 31689242 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-95024

Identifier Type: -

Identifier Source: secondary_id

NCI-V95-0685

Identifier Type: -

Identifier Source: secondary_id

95-024

Identifier Type: -

Identifier Source: org_study_id

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