Safety and Effectiveness of EBV-specific Cytotoxic T Cells for the Treatment for EBV Lymphomas or Other EBV-associated Malignancies

Inclusion Criteria

• •Three cohorts of patients will be eligible for enrollment:
• •°Cohort 1
• •Patients after allogeneic HCT who have:
• •1. EBV+ malignancies
• •2. EBV viremia (as evidenced by two serial plasma EBV DNA assays) without EBV+ malignancy
• •Included in cohort 1 will be patients with underlying immunodeficiency syndromes with:
• •3\. EBV+ malignancies 4. EBV viremia without current but with a history of prior EBV+ malignancy
• •Cohort 2
• •* Patients after allogeneic SOT who have:
• •1. EBV+ malignancies
• •2. EBV viremia (as evidenced by two serial plasma EBV DNA assays) without current but with a history of prior EBV+ malignancy.
• •* Patients in Cohort 1 (D) and 2 (B) treated for EBV viremia without evidence of EBV+ malignancy will need to have a history of a prior EBV malignancy with:
• •* Continued viremia at the completion of planned therapy
• •* Recurrence of viremia within 2 months from completion of planned therapy
• •* High grade viremia (\>20,000 copies) after treatment for EBV malignancy
• •* Evidence of EBV positivity for patients in cohort 1 and 2 is determined as follows:
• •* A biopsy showing EBV+ malignancy or
• •* A combination of EBV viremia AND radiographic appearance consistent with an EBV+ malignancy
• •Cohort 3
• •A. EBV-associated lymphomas and lymphoproliferative disorders not associated with immunodeficiency (biopsy required) (e.g. EBV+ Hodgkin lymphoma, etc).
• •\- Based on prior studies, patients with NK/T lymphoma will only be eligible for protocol if EBV-CTL therapy is being administered from their HCT donor either prior to or after HCT.
• •B. Other EBV-associated malignancies (biopsy required) including nasopharyngeal carcinoma, EBV+ gastric cancer, EBV+ leiomyosarcoma.
• •Patients in cohort 3 will be assessed for whether alternative standard therapy is available prior to being consented to the trial.
• •Patients in cohort 3 will need a biopsy showing EBV+ disease.
• •Patients in cohort 3 will not be treated for viremia alone.
• •All Patients:
• •1. Availability of EBV-CTLs generated specifically for the patient and demonstrated to be restricted by a shared HLA-allele.
• •2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for patients aged \> 16 years; Lansky score ≥ 20 for patients ≤ 16 years
• •3. For patients with PTLD in the alloHCT setting, the underlying disease for which alloHCT transplant was performed is either an EBV+ malignancy or in morphologic remission
• •4. Adequate organ function per the following (unless deemed to be caused by the underlying EBV-driven process which EBV-CTLs are intended to treat, or its prior therapy):
• •A. Absolute neutrophil count ≥ 500/μL, with or without cytokine support B. Platelet count ≥ 20,000/μL, with or without transfusion support C. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3× the upper limit of normal (ULN) and total bilirubin \< 2.5×ULN; D. Creatinine \< 3×ULN
• •5. Patient or patient's representative is willing and able to provide written informed consent