Clinical trial NCT03184753: Genetically Modified T Cells Against Ovarian Cancer
Official title: Innovative Treatment of Ovarian Cancer Based on Immunogene-modified T Cells (IgT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Keywords: Autologous
IgT
Ovarian Cancer
CART
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives are to evaluate the safety and efficacy of infusion of autologous ovarian cancer immunogene-modified T cells (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.

Eligibility criteria: 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.

Primary outcomes:
measure: percentage of adverse effects after OC-IgT cells injection
timeFrame: up to one month
Secondary outcomes:
measure: Rate of successful OC-IgT generation
timeFrame: up to one month
measure: Ability of OC-IgT cells to induce anti-ovarian cancer reaction
timeFrame: after 1 month from OC-IgT cells infusion until 12 months after infusion
measure: Ability of OC-IgT cells for anti-ovarian cancer reaction
timeFrame: after 1 month from OC-IgT cell infusion until 24 months after infusion
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References: