CELL INTELLIGENCE · 肿瘤细胞治疗研究

1. INCLUSION CRITERIA AT TIME OF PROCUREMENT

   1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non Hodgkin's Lymphoma, (regardless of the histological subtype) or EBV (associated)- T/NK-lymphoproliferative disease who may subsequently be eligible for the treatment component
   2. EBV positive tumor (can be pending)
   3. Weighs at least 10 kg
   4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given a copy of informed consent.
2. INCLUSION CRITERIA AT TIME OF INFUSION

   1\) Any patient regardless of age or sex, with diagnosis of either
   1. EBV positive Hodgkin's lymphoma
   2. EBV positive non-Hodgkin's Lymphoma (regardless of histologic subtype)
   3. EBV (associated)-T/NK-lymphoproliferative disease

   AND either

   A) In first or subsequent relapse or with persistent active disease despite therapy; OR

   B) With active disease if immunosuppressive chemotherapy is contraindicated as determined by the study PI, in consultation with the primary provider as needed, e.g. patients who develop Hodgkin's disease after solid organ transplantation or if the lymphoma is a second malignancy, e.g. a Richter's transformation of CLL.

   2\) EBV positive tumor confirmed by pathology

   3\) Patients with life expectancy ≥ 6 weeks

   4\) Patients with bilirubin ≤ 3x upper limit of normal, AST ≤ 3x upper limit of normal, creatinine ≤ 2x upper limit of normal for age and Hgb ≥ 7.0 (may be a transfused value)

   5\) Pulse oximetry of \>90% on room air

   6\) Patients should have been off other investigational therapy for 4 weeks prior to entry in this study.

   7\) Patients with a Karnofsky/Lansky score of ≥ 50

   8\) Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given a copy of informed consent.
3. EXCLUSION CRITERIA AT TIME OF PROCUREMENT

   1\. Known pregnancy or actively breastfeeding (pregnancy test is not required at the time of procurement).
4. EXCLUSION CRITERIA AT TIME OF INFUSION

   1. Pregnant or breastfeeding
   2. Active and uncontrolled bacterial, viral or fungal infection
   3. Current use of systemic corticosteroids (prednisone equivalent \>0.5 mg/kg/day)
   4. Bulky disease resulting in airway obstruction or risk for airway obstruction with further enlargement.

主要终点：1. Dose limiting toxicity rate (DLT) by Common Terminology Criteria for Adverse Events v5.0 · Dose-limiting toxicity is defined as any irreversible, life threatening or non-hematologic Grade 3-5 event considered to be primarily related to the EBVST infusion, with the exception of Grade 3-4 expected reactions such as fever and hypotension/ Grade 3-4 CRS toxicity persistent beyond 72 hours. · 28 days post infusion
次要终点：1. Response rate by Lymphoma Response to Immunomodulatory Therapy (LYRIC) criteria

• Arm A: Treatment without lymphodepletion chemotherapy · EXPERIMENTAL · C7R-EBVSTs Group B will be activated if only limited expansion and clinical efficacy is observed in Group A
• Arm B: Treatment with lymphodepletion chemotherapy · EXPERIMENTAL · C7R-EBVSTs with lymphodepletion chemotherapy

This study is for patients that have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease which has come back or has not gone away after treatment, including the best treatment the investigators know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that is sometimes called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. The investigators have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses. The investigators think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study the investigators will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. The investigators know that T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. The investigators have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on cancer.