CT Antigen TCR-redirected T Cells for Ovarian Cancer.

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Adaptimmune
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01567891
First received: March 16, 2012
Last updated: June 9, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Biological: NY-ESO-1c259 T cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 10
Study Start Date: June 2013
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567891

Contacts
Contact: RPCI Hotline 877-275-7724 askrpci@roswellpark.org

Locations
United States, California
City of Hope National Medical Center Recruiting
Durate, California, United States, 91010
Contact: Mihaela Cristea, MD    626-256-4673 ext 63155    mcristea@coh.org   
Principal Investigator: Mihaela Cristea, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Kunle Odunsi, MD, PhD    716-845-3497    Kunle.Odunsi@roswellpark.org   
Principal Investigator: Kunle Odunsi, MD, PhD         
Sponsors and Collaborators
Adaptimmune
Investigators
Study Chair: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01567891     History of Changes
Other Study ID Numbers: ADP-0011-001, 230612
Study First Received: March 16, 2012
Last Updated: June 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Ovarian Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on July 07, 2015