CT Antigen TCR-redirected T Cells for Ovarian Cancer.
Ovarian Cancer
Conditions: official terms
Ovarian Neoplasms
Conditions: Keywords
Ovarian Cancer
Study Type
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: NY-ESO-1c259 T cells
Type: Biological
Overall Status
This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.
Detailed Description
This is an open label clinical trial. Patients with the HLA-A201 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1c259 T. The trial is conducted entirely with outpatient procedures; however, patients may be hospitalized for the cytoreductive chemotherapy at the discretion of the investigator. Upon enrollment, patients will undergo leukapheresis for T cell collection, and their cells will be genetically engineered and expanded ex vivo. Seven days prior to receiving T-cells patients will undergo a cyclophosphamide conditioning regimen to potentiate the immunotherapy. The cell product will be infused as a split infusion (30% Day 0 and 70% Day 1; typically Monday and Tuesday) to mitigate risks associated with unanticipated infusion reactions. Patients will be followed daily for the first week, weekly until 4 weeks, 8 weeks, and 12 weeks and then at 6 months and 9 months. Patients will undergo disease monitoring by MRI/CT scan (as appropriate for disease) at baseline, day 28, 8 weeks and 12 weeks, and months 6, and 9 or until progression, whichever comes first. Optional tumor biopsies will be taken at baseline, at Day 28, and upon progression, if applicable.

In patients who have progressive disease following initial infusion but whose tumors continue to express NY-ESO-1, these patients may be eligible for a second infusion with redirected T cells.

At 9 months, the interventional portion of the protocol ends and long term follow‐up (LTFU) begins at 1 year, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Must have a diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum resistant disease and/or have received ≥ 2 lines of chemotherapy

- ≥ 18 years of age

- No significant immunodeficiency

- Have been informed of other treatment options

- Must be HLA-A201 positive

- Patient's tumor must be positive by histological or molecular assay for NY-ESO-1.

- ECOG performance status of 0 or 1

- Life expectancy of > 4 months

- At least 4 weeks from prior immunotherapy, or prior investigational agents.

- Measurable disease as defined by RECIST Criteria (V1.1)

- Must have adequate venous access for apheresis.

- Women of childbearing potential are requested to use acceptable methods of birth control for the duration of the study and until persistence of the study drug is no longer detected in the patient. This may be several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception. It is recommended that a combination of two methods be used.

- Patient must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Patients must have normal organ and marrow function as defined below:

- Leukocytes ≥ 3,000/mcL

- Absolute Neutrophil Count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Total bilirubin ≤ 1.5 ULN

- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal

- creatinine ≤ 2.0 mg/dL OR

- creatinine clearance > 60 mL/min for patients with creatinine levels above institutional normal

Exclusion Criteria:

- Currently receiving any other investigational agents

- Patients with active brain metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study

- Prior malignancy (except non-melanoma skin cancer) within 18 months of study entry NOTE: Patients must be in complete remission from prior malignancy in order to be eligible to enter the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g. interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to study entry. NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects are prescribed a brief course of oral corticosteroids, the use should be limited to less than 7 days. Use of steroids before apheresis and immune assessment blood draws should be discouraged as it will affect white blood cell function.

- Active infection with HIV, HBV or HCV

- Receipt of an experimental vaccine within 2 months or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months, or has received any previous gene therapy using an integrating vector

- History of severe autoimmune disease requiring steroids or other immunosuppressive treatments

- Lack of availability of a patient for immunological and clinical follow-up assessment

- Evidence or history of significant cardiac disease
City of Hope National Medical Center
Durate, California, United States
Status: Recruiting
Contact: Mihaela Cristea, MD - 626-256-4673 - mcristea@coh.org
Roswell Park Cancer Institute
Buffalo, New York, United States
Status: Recruiting
Contact: Kunle Odunsi, MD, PhD - 716-845-3497 - Kunle.Odunsi@roswellpark.org
Start Date
June 2013
Completion Date
January 2019
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page