CT Antigen TCR-redirected T Cells for Ovarian Cancer.

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Adaptimmune
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01567891
First received: March 16, 2012
Last updated: June 30, 2016
Last verified: June 2016
  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: NYESO-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 disease progression, 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 every 3 months until disease progression, 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 2017 (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, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NYESO-1c259 T cells.
Biological: NYESO-1c259 T cells
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Patients will receive at least 1x10⁹ transduced cells, however the target dose for this protocol is for patients to receive 5x10⁹ transduced cells with a maximum possible dose of 6x10⁹ administered as a single intravenous (IV) infusion.

Detailed Description:
This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1ᶜ²⁵⁹T. 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 single infusion (Day 0, typically Monday) 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 every 3 months until disease progression. 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 every 3 months until progression. Tumor biopsies will be taken at baseline, Week 8, and upon progression. 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 disease progression, the interventional portion of the protocol ends and long term follow-up (LTFU) begins, 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   (Adult, Senior)
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
  • Age ≥ 18 years of age
  • No significant immunodeficiency
  • Have been informed of other treatment options
  • Must be HLA A*0201, HLA-A*0205, and/or HLA-A*0206 positive by high resolution testing.
  • Patient's tumor must be positive by histological assay for NY-ESO-1ᶜ²⁵⁹T, according to the screening algorithm as described in Section 3.3.1. Positive expression is defined as ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry
  • ECOG performance status of 0 or 1
  • Life expectancy of > 4 months
  • Prior therapies:

    1. prior immunotherapy, or prior investigational agents should be washed out 4 weeks before apheresis and must be completed 4 weeks prior to pre-infusion lymphodepletive chemotherapy.
    2. monoclonal antibody therapy must be completed at least 6 weeks prior to pre-infusion lymphodepletive chemotherapy
    3. All previous cytotoxic chemotherapy, monoclonal antibody therapy, immune therapy should be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
    4. Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy
    5. Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week before apheresis and must be completed at least 1 week prior to pre-infusion lymphodepletive chemotherapy.
    6. Any grade 3 or 4 -hematologic toxicity of previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
  • Must have measurable disease as defined by RECIST 1.1.
  • 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 a period of 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.

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
  • 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.

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         
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305
Contact    650-498-0624    agonlez@stanford.edu   
Principal Investigator: Oliver Dorigo, MD, PhD         
United States, Florida
University of Miami, Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact       c.grandas@med.miami.edu   
Principal Investigator: Brian M Slomovitz, 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         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-563-4598    SESharafi@mdanderson.org   
Principal Investigator: Amir Jazaeri, MD         
Sponsors and Collaborators
Adaptimmune
Investigators
Study Chair: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute
  More Information

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 30, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Ovarian Cancer

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

ClinicalTrials.gov processed this record on July 28, 2016