Clinical Trials /

CT Antigen TCR-redirected T Cells for Ovarian Cancer.

NCT01567891

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CT Antigen TCR-redirected T Cells for Ovarian Cancer.
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: ADP-0011-001
  • SECONDARY ID: 230612
  • NCT ID: NCT01567891

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
NYESO-1c259 T cellsCohort 1

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalThis 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.
  • NYESO-1c259 T cells

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events Related to Study Treatment
Time Frame:Up to 12 months
Safety Issue:
Description:Number of Participants with Adverse Events related to study treatment

Secondary Outcome Measures

Measure:Tumor Response
Time Frame:Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression
Safety Issue:
Description:Number of participants with response as assessed by Immune-related Response Criteria (irRC)
Measure:Peak Persistence of Modified T-cells in the Peripheral Blood
Time Frame:Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU
Safety Issue:
Description:Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
Measure:Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood.
Time Frame:Weeks 4 and 8 post T-cell infusion
Safety Issue:
Description:Percentage of CD4+pentamer+ or CD8+pentamer+ cells expressing LAG-3, PD-1, TIM-3 in the functionality of NY-ESO-1ᶜ²⁵⁹T cells in the manufactured product and post-treatment blood.
Measure:Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein
Time Frame:Screening and at Baseline
Safety Issue:
Description:NY-ESO-1 expression as determined by Histoscore (H score). Histoscore (0-300) represents the amount of NY-ESO-1 protein present in the tissue sample. H-Score formula: [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)] (It is not clearly established if NY-ESO-1 H score has an association with prognosis.)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Adaptimmune

Trial Keywords

  • Ovarian Cancer
  • Cell Therapy
  • T Cell Therapy
  • NY-ESO-1
  • Immuno-oncology
  • Metastatic
  • Previously treated
  • T Cell Receptor

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