Engineered Immune Effectors Against Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT03362606
• Recruitment Status: Unknown
• First Posted: December 5, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Study Description

Brief Summary:

This is a single-arm, open-label, phase I/II trial to evaluate the safety and efficacy of ovarian cancer specific cytotoxic lymphocytes (OC-CTLs) in women.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Biological: OC-CTLs	Phase 1; Phase 2

Detailed Description:

Ovarian cancer is a cancer that forms in or on an ovary. The majority of ovarian cancers arise from the epithelium (outer lining) of the ovary. In 2015 it was reported found in 1.2 million women and resulted in 161,100 deaths worldwide. Among women it is the seventh-most common cancer and the eighth-most common cause of death from cancer. Treatment for ovarian cancer consists of surgery, chemotherapy, immunotherapy and sometimes, radiotherapy. The kind of treatment depends on many factors, including the type of ovarian cancer, its stage and grade, as well as the general health of the patient.

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 ovarian cancer specific cytotoxic T lymphocytes in patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intervention of Ovarian Cancer Based on Engineered Immune Effectors (EIEs)
• Actual Study Start Date: November 15, 2017
• Actual Primary Completion Date: January 31, 2019
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: OC-CTLs; Autologous ovarian cancer specific cytotoxic lymphocytes	Biological: OC-CTLs; 2 to 4 infusions, once a week, for 1x10^5~4x10^6 CTLs/kg via IV, abdominal cavity or tumor injection each time

Outcome Measures

Primary Outcome Measures :

1. Safety of OC-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 6 months ]
   Physiological parameter (measuring cytokine response, fever, symptoms)

Secondary Outcome Measures :

1. Functional analyses of OC-CTLs in vitro [ Time Frame: 4 weeks ]
   The specificity of OC-CTLs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT).
2. Anti-tumor effects [ Time Frame: 1 year ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 80 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage II-IV.
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. Patients with ovarian tumors with low malignant potential (i.e. borderline tumors);
2. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
3. Previous treatment of adoptive T cell therapy.
4. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug
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 infected with HCV (HCV antibody positive), HBV (HBsAg positive), and HIV (HIV antibody positive),Treponema pallidum antibody positive or TB culture positive.

Contacts and Locations

Contacts

Contact: Lung-Ji Chang, PhD; 86-075586725195; c@szgimi.org

Locations

China, Guangdong

Jinshazhou Hospital of Guangzhou University of Chinese Medicine; Recruiting

Guangzhou, Guangdong, China, 510415

Contact: Qichun Cai, MD 86-13802830754

Shenzhen Geno-immune Medical Institute; Recruiting

Shenzhen, Guangdong, China, 518000

Contact: Lung-Ji Chang, PhD 86-075586725195 c@szgimi.org

China, Yunnan

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

Kunming, Yunnan, China, 650000

Contact: Xun Lai, MD 13577096609 1729112214@qq.com

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

• Principal Investigator: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute
• Study Director: Qichun Cai, MD; Jinshazhou Hospital of Guangzhou University of Chinese Medicine
• Study Director: Xun Lai, MD; Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

More Information

• Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT03362606
• Other Study ID Numbers: GIMI-IRB-17018
• First Posted: December 5, 2017
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:

Ovarian cancer; Cytotoxic lymphocyte; OC-CTL

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type