Clinical trial NCT03415100: Pilot Study of NKG2D-Ligand Targeted CAR-NK Cells in Patients With Metastatic Solid Tumours
Official title: Pilot Study of NKG2D-Ligand Targeted CAR-NK Cells in Patients With Metastatic Solid Tumours
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumours
Lead sponsor: The Third Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2018-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-centre, single arm, open-label pilot study to evaluate the safety and feasibility of CAR-NK cell treatment in subjects with metastatic solid tumours. Autologous or allogeneic NK cells are transfected by mRNA electroporation to prepare investigational CAR-NK cells with transiently enhanced specificity and activity against NKG2D-ligand expressing cancer cells.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any research procedure.
2. Histologically or cytologically confirmed diagnosis of metastatic solid tumours
3. ECOG performance status of 0-3;
4. Adequate organ function defined as: ANC≥1.0×10\^9/L, PLT≥75×10\^9/L, ALB≥25g/L, TBIL≤1.5×ULN, AST≤2.5×ULN, ALT≤2.5×ULN, ALP≤2.5×ULN, Cr≤1.5×ULN;
5. The patient's own PBMCs or PBMCs from a biological parent or child who is willing to donate blood will be used to prepare CAR-NK cells. The parent or child should be ≥18 and ≤60 years old, and he or she is able to sign the informed consent for blood donation by himself/herself;
6. Patients who won't benefit from surgery, or refuse surgical treatment; patients who won't benefit from chemotherapy, can't tolerate chemotherapy or refuse chemotherapy.
7. Patients volunteer to participate in this study and sign the informed consent form for subjects;
8. Blood donors sign the informed consent form for blood donors.
9. Blood donors have negative test results for HIV, HBV and HCV;
10. If a subject or blood donor is a female of childbearing potential, she must have a negative urine pregnancy test result.

Exclusion Criteria:

1. Patients who are suffering from uncontrollable or active infectious diseases of the hematological system, cardiovascular system, respiratory system, digestive system, urinary system, or the endocrine system;
2. Patients with immunologic deficiency or autoimmune diseases;
3. Patients with severe hypersensitivity reactions;
4. Patients received other forms of cellular therapies within the last 3 months;
5. Patients received systemic steroids within the last 3 months;
6. Patients who are breastfeeding or pregnant;
7. Patients with brain metastases;
8. Patients who have received an organ transplant.

Primary outcomes:
measure: Number of Adverse Events
timeFrame: from day 0 - month 4
Secondary outcomes:
measure: Anti-tumour response due to CAR-NK cell infusions
timeFrame: 100 days after CAR-NK cell infusion
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Third Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The Third Affiliated Hospital of Guangzhou Medical University
name: Xuehu Xu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ng YY, Du Z, Zhang X, Chng WJ, Wang S. CXCR4 and anti-BCMA CAR co-modified natural killer cells suppress multiple myeloma progression in a xenograft mouse model. Cancer Gene Ther. 2022 May;29(5):475-483. doi: 10.1038/s41417-021-00365-x. Epub 2021 Sep 1.