γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Preliminary Exploration of γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL).

This study aims to evaluate the safety and efficacy of autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.

This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, screening and registration to the trial, apheresis, γδT cells preparation, pre-treatment for lymphodepleting chemotherapy (selectable plan), treatment and follow-up. The study will evaluate the safety and efficacy of the autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.

Inclusion Criteria:

1. Patients should sign informed consent form voluntarily.
2. Gender unlimited, age ≥ 18 years old.
3. Patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma(PTCL) expect for γδT lymphoma.
4. Patients had an evaluable imaging lesion of at least greater than 1.5 cm (except CLL).
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
6. Adequate bone marrow function as defined by：Absolute neutrophil count (ANC) >1000/mm3；Absolute lymphocyte count (ALC) ≥300/mm3；Platelet ≥50000/mm3；Hemoglobin >8.0g/dl.
7. Adequate end organ function as defined by: Total bilirubin ≤ 2 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 60ml/min.
8. Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study.

Exclusion Criteria:

1. Patients with history of allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

2. Active central nervous system (CNS) lymphoma; Patients with symptoms of CNS disease must undergo lumbar puncture and brain nuclear magnetic resonance to exclude CNS lymphoma.

3. Patients receiving chemotherapy within 2 weeks prior to γδT cell infusion, with the following exceptions:

   • Pretreatment chemotherapy prescribed by the protocol
   • In order to prevent CNS intrathecal chemotherapy (should be stopped 1 week before γδT cell therapy)
   • Other exploratory combined medications

4. Patients with systemic vasculitis, or with active or uncontrolled autoimmune diseases, as well as primary or secondary immunodeficiency diseases.

5. Active chronic hepatitis B or hepatitis C virus infection, active cytomegalovirus (CMV), EBV infection.

6. Major surgery that was evaluated by the investigator as unsuitable for inclusion within 4 weeks prior to screening.

7. History of other malignant tumors, with the following exceptions

   • Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)
   • Cured situ carcinoma (e.g. cervical carcinoma)
   • Localized prostate cancer with radiotherapy or surgery
   • Patients with a history of malignant tumors, but the disease has been cured for ≥2 years

8. Patient's cardiac function meets any of the following conditions

   • Left ventricular ejection fraction (LVEF) ≤45%
   • Class III or IV heart failure according to the NYHA Heart Failure Classifications
   • QTcB>450 msec
   • Other cardiac disease that investigators judge is not suitable for enrollment

9. History of epilepsy or other active central nervous system disorders.

10. Inoculated live vaccine within 6 weeks before screening.

11. Uncontrolled serious active infection (such as sepsis, bacteremia and fungemia).

12. Patients are allergic to cytokines.

13. Expected survival < 12 weeks.

14. Participated in any other interventional clinical trial within three months.

15. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.