γδt cells immunotherapy in patients with relapsed or refractory non-hodgkin's lymphoma (nhl)

Conditions: Non-Hodgkin's Lymphoma; Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma; Chronic Lymphoblastic Leukemia; Peripheral T Cell Lymphoma

Summary: 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.

Eligibility criteria:
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.