CT Antigen TCR-redirected T Cells for Ovarian Cancer.

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Adaptimmune
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: March 16, 2012
Last updated: June 9, 2015
Last verified: June 2015

March 16, 2012
June 9, 2015
June 2013
July 2016   (final data collection date for primary outcome measure)
NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: At apheresis: Day -30 (±10 days) until month 9, LTFU (Years 1-15) ] [ Designated as safety issue: Yes ]
To determine the safety and tolerability of autologous redirected T cell therapy in patients with treatment refractory or resistant Stage III/IV ovarian cancer.
NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: Month: 9 ] [ Designated as safety issue: Yes ]
This will evaluate safety of autologous genetically modified T cells transduced to express the high affinity MAGE-A3a3a TCR in HLA-A101 subjects, and the high affinity NY-ESO-1c259 TCR in HLA-A201 subjects.
Complete list of historical versions of study NCT01567891 on ClinicalTrials.gov Archive Site
Tumor Response [ Time Frame: Baseline, Day 28, 8 weeks and at Months 3, 6, and 9, LTFU (Years 1-15) ] [ Designated as safety issue: No ]
Evaluate correlates of treatment efficacy by measuring 1) Clinical response rates to treatment based on irRC and progression free survival, 2) to evaluate the persistence of genetically modified cells in the peripheral blood, and as possible at tumor sites, and 3) to evaluate the phenotype and functionality of genetically modified cells isolated from peripheral blood and, as possible, from tumor sites post infusion.
Tumor Measurements [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
To measure the effect of MAGE-A3a3a-T and NY-ESO-1c259-T on tumor as measured by Immune-related Response Criteria and progression free survival
Not Provided
Not Provided
CT Antigen TCR-redirected T Cells for Ovarian Cancer.
A Phase I/IIa, Open Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Patients With Recurrent or Treatment Refractory Ovarian Cancer.

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.

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.

Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Ovarian Cancer
Biological: NY-ESO-1c259 T cells
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. A total dose of 0.5-1e10 total cells will be administered on consecutive days as a split dose of 30% (Day 0) and 70% (Day 1) by intravenous (IV) infusion.
Experimental: Cohort 1
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 cells.
Intervention: Biological: NY-ESO-1c259 T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
January 2019
July 2016   (final data collection date for primary outcome measure)

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
18 Years and older
Contact: RPCI Hotline 877-275-7724 askrpci@roswellpark.org
United States
ADP-0011-001, 230612
Not Provided
Study Chair: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP