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Safety Study of Cord Blood-derived Cytokine-induced Killer Cells in Patients With Solid Tumor After Radical Resection

Phase 1
Conditions
Lung Cancer
Hepatocellular Carcinoma
Renal Cell Carcinoma
Registration Number
NCT01914263
Lead Sponsor
Alliancells-PuRui Biocience Co., Ltd.
Brief Summary

Cytokine-induced killer (CIK) cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which present a mixed T-NK phenotype and are endowed with a major histocompatibility complex-unrestricted antitumor activity. Radical surgery is a good therapy for patients with solid tumor.However, tumor relapse is still a risk for those patients. Our hypothsis is that cytokine induced killer cells maybe decrease the recurrence rate. The purpose of this study is to evaluate the safety and tolerability of cord blood-derived cytokine induced killer cells in patients with solid tumor following radical resection.

Detailed Description

It was estimated that 2.6 million people suffer from cancer and 1.8 million die of cancer in China yearly according to the Annual Report of Cancer Registration in China 2012. So far, the main treatment modalities for tumors have been surgery, radiotherapy and chemotherapy. However, tumor relapse is still a risk for those patients underwent the conventional therapy. 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. Cytokine-induced killer (CIK) cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which present a mixed T-NK phenotype and are endowed with a MHC-unrestricted antitumor activity. CIK cells are expanded conventionally from peripheral blood mononuclear cells by addition of a variety of cytokines in vitro culture.

Autologous CIK cells infusion therapy for patients with malignancies is reported world widely. However, there are several drawbacks for autologous CIK limiting its clinical application. For example, limited cell numbers, decreased cell activities, and unavailable in time etc. Cord blood, as a novel source of non-senescent lymphocytes for tumor immunotherapy, has been focused on recently. Accumulating preclinical studies have shown that cord blood-derived CIK cells are potent anti-tumor effectors using in adoptive cancer immunotherapy. However it is unclear whether administration of cord blood-derived CIK cells is safe in patients with malignancies. Our previous studies demonstrated that clinical scale expansion of CIK from cord blood is feasible. The cord blood-derived CIK cells exhibit antitumor effect in vitro and in vivo (tumor bearing nude mice) against a variety of tumor cells including ZR751, MCF7, HepG2, SMMC-7721, Hela, A375, DU145, H1299 and A549. Furthermore, intravenous infusion of a single dose of 3X10\^8 cord blood-derived CIK cells in mice is safe.

The purpose of this study is to evaluate the safety and tolerability of cord blood-derived CIK cells in patients with solid tumor following radical resection.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Male or female patients over 18 years of age.
  • Patients who give written informed consent.
  • Patients with solid tumor already had radical resection
  • Definition of radical resection in this study:
  • All tumors were moved out, with a clean resection margin.
  • No distance metastasis.
  • No major post-operative complication.
  • Without any anti-cancer medication within the past 15 days.
  • The following laboratory parameters: Platelet count >= 70 x 109/L; Hemoglobin >= 8.5 g/dL; Albumin >= 3.5 g/dL; Total bilirubin <= 25umol/L; Alanine transaminase (ALT) and AST <= 2.5 x upper limit of normal; Serum creatinine <= 1.5 x the upper limit of normal; Prothrombin time (PT) <= 3 seconds above control.
Exclusion Criteria
  • History of cardiac disease.
  • Active clinically serious infections
  • Known history of human immunodeficiency virus (HIV) infection
  • Known Central Nervous System tumors including metastatic brain disease.
  • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
  • History of organ allograft.
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial.
  • Pregnant or breast-feeding patients.
  • Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
  • Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
The incidence of adverse events following infusion of cord blood-derived cytokine-induced killer cells.30 days post-infusion

The primary outcome measures for safety will include the incidence of fever,chill,rash and Graft-versus-Host Disease (GVHD).

Secondary Outcome Measures
NameTimeMethod
HaematologyBaseline, 1 day, 3 days 10 days and 30 days after cell infusion

These parameters include erythrocytes, leukocytes, platelets, T cell, B cell, Natural killer cell, CD4/CD8, Th1/Th2, Th17 cell and Treg cell.

Serological analysisBaseline, 1day, 3 days 10 days and 30 days after cell infusion

immunoglobulin G, immunoglobulin A, immunoglobulin D, immunoglobulin E and immunoglobulin M. Albumin (ALB), Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), Prealbumin(PA), total bilirubin (TB), and direct bilirubin (DB); Blood urea nitrogen(BUN), Urea (UA), and Crea (Cr); Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-C), and Non-HDL-C; blood sugar;

Trial Locations

Locations (3)

Hannan BOAO Life infinity international anti-aging medical center

🇨🇳

Qionghai, Hainan, China

The 210 Hospital of Chinese People's Liberation Army

🇨🇳

Dalian, Liaoning, China

The 323 Hospital of Chinese People's Liberation Army

🇨🇳

Xi'an, Shaanxi, China

Hannan BOAO Life infinity international anti-aging medical center
🇨🇳Qionghai, Hainan, China

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