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

Tracking Information

• First Submitted Date: November 20, 2017
• First Posted Date: December 5, 2017
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: November 15, 2017
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2017)

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 29, 2017)

• 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).
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Engineered Immune Effectors Against Ovarian Cancer
• Official Title: Intervention of Ovarian Cancer Based on Engineered Immune Effectors (EIEs)
• 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.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

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

Study Arms

Experimental: OC-CTLs

Autologous ovarian cancer specific cytotoxic lymphocytes

Intervention: Biological: OC-CTLs

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 29, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

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. 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 10 Years to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03362606
• Other Study ID Numbers: GIMI-IRB-17018
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019