Genetically Modified T Cells Against Ovarian Cancer

Innovative Treatment of Ovarian Cancer Based on Immunogene-modified T Cells (IgT)

The primary objectives are to evaluate the safety and efficacy of infusion of autologous ovarian cancer immunogene-modified T cells (OC-IgT cells).

Study Overview

• Status: Unknown
• Conditions: Ovarian Cancer
• Intervention / Treatment: Biological: OC-IgT cells

Detailed Description

Ovarian cancer (OC) is a cancer that forms in or on an ovary. The majority of OC arises from the epithelium (outer lining) of the ovary. In 2015 OC was 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 OC consists of surgery, chemotherapy, radiotherapy and sometimes, novel immunotherapies. The best treatment options depend on many factors, including the type of OC, its stage and grade, as well as the general health of the patient.

Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific antigens has proven to be effective. Novel chimeric antigen receptor gene modified T cell (CART) based immunotherapy has demonstrated great successes in B cell malignancies. Here, the study aim is to evaluate the safety and efficacy of genetically engineered OC-specific and immune modulatory T cells in patients. The primary study objectives are to evaluate the safety of the investigational product, autologous OC-IgT cells, to subjects by IV and intratumoral injection. The secondary study objectives are (1) to evaluate the success rate of generating autologous OC-IgT cells in vitro, and (2) to determine the anti-OC efficacy of the OC-IgT cells.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-Immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Written, informed consent obtained prior to any study-specific procedures.
2. Female patients ≥ 20 years.
3. Eastern Cooperative Oncology Group (ECOG) PS of 0, 1 or 2.
4. Life expectancy ≥ 3 months.
5. Able to comply with the protocol.

6. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage III-IV.

   • Complete remission after salvage treatment for first recurrence.
7. Not pregnant, and on appropriate birth control if of childbearing potential.

8. Adequate bone marrow reserve with ·absolute neutrophil count (ANC) ≥ 1000/mm3.

   ·Platelets ≥100,000/mm3.

9. Adequate renal and hepatic function with ·Serum creatinine ≤ 2 x upper limit of normal (ULN). ·Serum bilirubin ≤ 2 x ULN.

   • aspartate aminotransferase (AST)/ALT ≤ 2 x ULN.
   • Alkaline phosphatase ≤ 5 x ULN.
   • Serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.

Exclusion Criteria:

1.Patients with:

• Non-epithelial ovarian cancer.
• Ovarian tumors with low malignant potential (i.e. borderline tumors).
• Synchronous primary endometrial carcinoma and ovarian cancer. 2.Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).

Previous experience of gene-engineered T cell therapy 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:

·Absolute neutrophil count < 1.0 x 109/L.

• Platelet count < 100 x 109/L.
• Hb < 9 g/dL. 8. Inadequate liver and renal function:
• 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 (or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases).
• 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 HIV (HIV 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: Single arm; OC-IgT cells to treat ovarian cancer.	Biological: OC-IgT cells; Autologous human OC-IgT cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of adverse effects after OC-IgT cells injection	To assess the safety of autologous OC-IgT cells in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria.	up to one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful OC-IgT generation	The percentage of successful OC-IgT generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one prepatation, will be evaluated.	up to one month
Ability of OC-IgT cells to induce anti-ovarian cancer reaction	measurement of CA125 concentration in blood sample	after 1 month from OC-IgT cells infusion until 12 months after infusion
Ability of OC-IgT cells for anti-ovarian cancer reaction	Objective response (complete response (CR) + partial response (PR)) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	after 1 month from OC-IgT cell infusion until 24 months after infusion

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2017
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: June 4, 2017
• First Submitted That Met QC Criteria: June 10, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Autologous; Ovarian Cancer; CART; IgT
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: GIMI-IRB-17002

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