Clinical Efficacy and Safety of NKT Cell Infusion in Patients With Advanced Solid Tumor

Minghui Zhang

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Gastric Cancer

Non-small Cell Lung Cancer

Hepatocellular Carcinoma

Colorectal Cancer

Treatments

Biological: natural killer T cell

Study type

Interventional

Funder types

Other

Identifiers

NCT02562963

BHXH-CA-150413 (Other Identifier)

SHAPHC-CA-150209 (Other Identifier)

NKT-THU2015

Details and patient eligibility

About

Natural killer T (NKT) cells are a unique subset of lymphocytes that present a mixed T-NK phenotype. Our hypothesis is that Natural killer T cells may decrease the tumor burden and improve overall survival. The purpose of this study is to determine whether Natural killer T (NKT) cells are effective and safe in the treatment of patients with unresectable advanced solid tumor.

Full description

According to the Annual Report of Cancer Registration in China 2014, lung cancer, gastric cancer, liver cancer and colorectal cancer have become the top 4 solid tumors with the highest morbidity and mortality rates. So far, the main treatment modalities for these tumors have been surgery, radiotherapy and chemotherapy. However, the effect of conventional therapy on advanced cancer is limited, tumor metastasis is the major cause of death in patients with advanced cancer. With the development of oncology and immunology in recent years, immunotherapy represents a novel path to obtain a durable and long-lasting response in cancer patients.

Natural killer T (NKT) cells are a unique subset of lymphocytes that present a mixed T-NK phenotype. NKT cells are expanded conventionally from peripheral blood mononuclear cells by addition of a variety of cytokines in vitro culture. Our previous studies demonstrated that the expansion of NKT cells in a clinical usage scale from peripheral blood mononuclear cells is feasible. Those expanded NKT cells exhibit antitumor effect in vitro and in vivo (tumor -bearing nude mice) against a variety of tumor cells. Furthermore, intravenous infusion of a single dose of 4X10^9 NKT cells in mice has been proved safe.

The purpose of this study is to evaluate the efficacy and safety of NKT cells in patients with unresectable advanced solid tumor.

Enrollment

120 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age: 18 to 75 years, Male or Female
Histological or cytologically diagnosis of advanced non-small cell lung cancer, or advanced gastric cancer, or advanced hepatocellular carcinoma, or advanced colorectal cancer
Patients' tumor tissue (formalin-fixed, paraffin-embedded) must be sufficient for diagnosis of cancer by a certified Laboratory of Pathology
Laboratory values within the following ranges prior to receiving treatment of study agent: Hemoglobin≧11.0 g/dL, Neutrophils count≧1.5×l09/L, Lymphocytes count≧lower limit of institutional normal, Platelet count≧80×l09/L, Serum creatinine≦2.0 mg/dL, Serum bilirubin≦2 x upper limit of institutional normal, AST/ALT≦2 x upper limit of institutional normal
No dyspnea at rest. Oxygen saturation ≥90% on room air
Able to tolerate apheresis procedure including placement of temporary apheresis catheter
No genetic disease
No chemotherapy and radiation therapy to be planned recently
Fertile females/males must consent to use contraceptives during participation of the trial. Women of child bearing potential must have a negative pregnancy test prior to receiving treatment of study agent within 7 days
Patients must have a Karnofsky performance status greater than or equal to 80%
Life expectancy greater than twelve months
Able and willing to give witnessed, written informed consent form prior to receiving any study related procedure
Agree that progress of the disease must be radiographically measurable by computerized tomography (CT) scanning technique or magnetic resonance imaging (MRI) (per RECIST1.1 criteria)
Agrees to participate in long-term follow-up for up to 3 years, if received NKT infusion

Exclusion criteria

Organ dysfunction defined as follows: Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure, myocardial infarction within the past six months, unstable angina, coronary angioplasty within the past six months, uncontrolled atrial or ventricular cardiac arrhythmias; Child-Pugh C; Renal function failure or uremia; Respiratory failure; Disturbance of consciousness
Suffering from lymphoma or leukemia
Serious infections requiring antibiotics, bleeding disorders
Patients with myelodysplastic syndrome (MDS)
History of immunodeficiency disease or autoimmune disease
Known or suspected allergy to the investigational agent or any agent given in association with this trial
Known central nervous system tumors including metastatic brain disease, unless treated and stable
Other malignancy within 3 years prior to entry into the study
Negative HIV antigen and antibody, Hepatitis B surface antigen and Hepatitis C PCR within 21 days prior to enrollment
Patients with chronic disease which is undergoing immune reagents or hormone therapy
Previous bone marrow or stem cell transplant, or organ allograft
Within concurrent chemotherapy
Concomitant treatment with corticosteroids (Topical or inhalational corticosteroids are permitted)
Concurrent other medical condition that would prevent the patient from undergoing protocol-based therapy
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent
Pregnant or breast-feeding patients
Mental impairment or addictive disorders that may compromise the ability to give informed consent
Lack of availability of a patient for immunological and clinical follow-up assessment