Engineered Immune Effectors Against Cervical Cancer

NCT ID: NCT03362619

Last Updated: 2019-09-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-15
• Study Completion Date: 2020-12-31

Brief Summary

The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.

Detailed Description

Cervical cancer (CC) is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of the cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, CC is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of CC consists of surgical intervention, radiation, chemotherapy and immunotherapy.

Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of CC-specific engineered immune effectors including cytotoxic T lymphocytes in patients.

Conditions

Cervical Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CC-EIEs

Autologous cervical cancer specific engineered immune effectors (EIEs)

Group Type: EXPERIMENTAL

CC-EIEs

Intervention Type: BIOLOGICAL

2 to 4 infusions, once a week, for 1x10\^5\~1x10\^7 CTLs/kg via IV, abdominal cavity or intratumoral injection each time

Interventions

CC-EIEs

2 to 4 infusions, once a week, for 1x10\^5\~1x10\^7 CTLs/kg via IV, abdominal cavity or intratumoral injection each time

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Written, informed consent obtained prior to any study-specific procedures.

2. Age older than 10 years.

3. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.

4. Expected survival ≥ 12 weeks.

5. Not pregnant, and on appropriate birth control if of childbearing potential.

6. Evidence of high-risk HPV infection.

7. Stage III-IV or recurrent cervical cancer.

8. Initial hematopoietic reconstitution with

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

9. 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.

10. Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test negative.

Exclusion Criteria

1. Patients with

• cervical benign lesions: cervical columnar epithelium ectopic, cervical polyps, cervical endometriosis and cervical tuberculous ulcers;
• cervical benign tumors: cervical submucous myoma, cervical cancer, cervical papilloma.

2. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).

3. Previous exposure to mouse SCC antibody.

4. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.

5. Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).

6. Pregnant or lactating females.

7. Inadequate bone marrow function with

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

8. 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.

9. Serious active infection requiring i.v. antibiotics at during screening.

10. Subject actively 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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Lung-Ji Chang

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Qichun Cai, MD

Role: STUDY_DIRECTOR

Jinshazhou Hospital of Guangzhou University of Chinese Medicine

Xun Lai, MD

Role: STUDY_DIRECTOR

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Locations

Jinshazhou Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, China

Site Status: RECRUITING

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Kunming, Yunnan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

86-075586725195

Facility Contacts

Qichun Cai, MD

Role: primary

86-13802830754

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-075586725195

Xun Lai, MD

Role: primary

1729112214@qq.com

13577096609

Other Identifiers

GIMI-IRB-17019

Identifier Type: -

Identifier Source: org_study_id