Clinical trial NCT04028440: γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)
Official title: Preliminary Exploration of γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL).
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Non-Hodgkin's Lymphoma
Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma
Chronic Lymphoblastic Leukemia
Peripheral T Cell Lymphoma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Beijing GD Initiative Cell Therapy Technology Co., Ltd.
name: Chinese Academy of Medical Sciences
First posted: 2019-07-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Biological: Autologous γδT cells Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Number of Participants with Severe/Adverse Events as a Measure of Safety.
timeFrame: 15 months
measure: Overall response rate (ORR)
timeFrame: 28 days after infusion of γδT cells
Secondary outcomes:
measure: Duration of remission (DOR)
timeFrame: 15 months
measure: Time to response(TTR)
timeFrame: 15 months
measure: Disease control rate (DCR)
timeFrame: 15 months
measure: Progression free survival (PFS)
timeFrame: 15 months
measure: Overall survival (OS)
timeFrame: 15 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Disease Hospital
name: Dehui Zou, Dr.
role: PRINCIPAL_INVESTIGATOR
References: