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

Atara Biotherapeutics

Status and phase: Completed; Phase 2; Phase 1

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

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

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00002663

MSKCC-95024

P30CA008748 (U.S. NIH Grant/Contract)

NCI-V95-0685

95-024

Details and patient eligibility

About

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.

Enrollment: 58 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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58 participants in 10 patient groups

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

Experimental group

Description:

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.

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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

EBV+ AID-LPD (Tab-cel Only)

Experimental group

Description:

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.

Treatment:

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

EBV+ LMS (Tab-cel Only)

Experimental group

Description:

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.

Treatment:

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

EBV+ NPC (Tab-cel Only)

Experimental group

Description:

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.

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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

EBV+ Viremia (EBV-CTLs Only)

Experimental group

Description:

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.

Treatment:

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

EBV+ PID-LPD (Tab-cel or EBV-CTLs)

Experimental group

Description:

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.

Treatment:

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

EBV+ Lymphoma (Tab-cel or EBV-CTLs)

Experimental group

Description:

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.

Treatment:

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