Intervention of Engineered Immune Effector T Cells Against Lung Cancer

Interventional Treatment of Lung Cancer (LC) With LC Specific Immune Lymphocytes (LC-CTLs)

The primary objective of this study is to evaluate the safety of lung cancer specific cytotoxic lymphocytes (LC-CTLs). The secondary objectives are to evaluate the rate of successful LC-CTLs generation in vitro and determine the anti-lung cancer efficacy.

Study Overview

• Status: Withdrawn
• Conditions: NSCLC; Lung Cancer
• Intervention / Treatment: Biological: LC-CTLs

Detailed Description

Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. The two main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). Worldwide in 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths. Common treatments include surgery, chemotherapy, and radiotherapy.

Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of lung cancer specific cytotoxic T lymphocytes cells in patients.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Geno-immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written, informed consent obtained prior to any study-specific procedures.
2. Age older than 18 years.
3. Patients with refractory, relapsed, metastatic, advanced lung cancer confirmed by histology and biopsy.
4. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
5. Expected survival ≥ 12 weeks.
6. Not pregnant, and on appropriate birth control if of childbearing potential.

7. Initial hematopoietic reconstitution with

   • neutrophils (ANC) ≥ 1,000/mm^3;
   • platelet (PLT) ≥ 100,000/mm^3.

8. Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

   • serum creatinine ≤ 2×ULN;
   • serum bilirubin ≤ 2×ULN;
   • AST/ALT ≤ 2×ULN;
   • ALKP ≤ 5×ULN;
   • serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.
9. Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test were negative.

Exclusion Criteria:

1. Have occurred in 5 years or are currently suffering from other cancers, except for cured cervical cancer, non-melanoma skin cancer and superficial bladder cancer.
2. Previous exposure to mouse CEA antibody.
3. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
4. Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).
5. Pregnant or lactating females.

6. Inadequate bone marrow function with

   • absolute neutrophil count < 1,000/mm^3;
   • platelet count < 100,000/mm^3;
   • Hb < 9 g/dL.

7. Inadequate liver and renal function with

   • serum (total) bilirubin > 1.5 x ULN;
   • AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases);
   • alkaline phosphatase > 2.5 x ULN;
   • serum creatinine >2.0 mg/dl (> 177 μmol/L);
   • urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
8. Serious active infection requiring i.v. antibiotics at during screening.
9. Subject infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LC-CTLs; Autologous lung cancer specific cytotoxic lymphocytes	Biological: LC-CTLs; 2 to 4 infusions, once a week, for 1x10^5~4x10^6 CTLs/kg via IV, chest or tumor injection each time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of LC-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional analyses of LC-CTLs in vitro	The specificity of LC-CTLs in vitro will be analysed by intracellular cytokine staining (ICCS) or enzyme-linked immunospot assay (ELISPOT).	2 weeks
Anti-tumor effects	Biochemical markers and image scan will be got before and after treatment. Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2018
• Last Update Submitted That Met QC Criteria: March 25, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: NSCLC; Lung cancer; Cytotoxic lymphocyte; LC-CTL
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: GIMI-IRB-17022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No