Clinical Trials /

Gene-Modified T Cells in Treating Patients With Locally Advanced or Stage IV Solid Tumors Expressing NY-ES0-1

NCT02650986

Description:

This phase I/IIa trial studies the side effects and best dose of a gene-modified T cells and to see how effective it is in treating patients with solid tumors expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread from where it started to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (metastatic). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then given them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading, and it may also allow genetically modified T cells to grow.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gene-Modified T Cells in Treating Patients With Locally Advanced or Stage IV Solid Tumors Expressing NY-ES0-1
  • Official Title: A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: I 258514
  • SECONDARY ID: NCI-2015-02080
  • SECONDARY ID: I 258514
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT02650986

Conditions

  • Adult Solid Neoplasm

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)
NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBLAnti-NY-ESO-1 TCR Retroviral Vector Transduced Autologous PBLTreatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)
TGFbDNRII-transduced Autologous Tumor Infiltrating LymphocytesTGFbDNRII-transduced Autologous TILsTreatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)

Purpose

This phase I/IIa trial studies the side effects and best dose of a gene-modified T cells and to see how effective it is in treating patients with solid tumors expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread from where it started to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (metastatic). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then given them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading, and it may also allow genetically modified T cells to grow.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety and feasibility of adoptive transfer of autologous NY-ESO-1 T cell
      receptor (TCR) (NY-ESO-1 reactive TCR retroviral vector transduced autologous
      PBL)/dominant-negative transforming growth factor-beta receptor II (dnTGFbetaRII)
      (TGFbDNRII-transduced autologous tumor infiltrating lymphocytes [TILs]) transgenic T cells in
      combination with Decitabine.

      SECONDARY OBJECTIVES:

      I. NY-ESO-1 TCR/ dnTGFβRII transgenic T cell persistence by analyzing serial peripheral blood
      samples for the presence of T cells with the NY-ESO-1 TCR by tetramer analysis.

      II. To study T cell differentiation that correlates with higher anti-tumor responses.

      III. Assess clinical response and progression free survival.

      OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs
      followed by a phase II study.

      Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients
      then receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL with
      TGFbDNRII-transduced autologous TILs infusion on day 0.

      After completion of study treatment, patients are follow up at weeks 1-4, 8 and 12, at 6 and
      9 months, every 6 months for 5 years, and yearly for 9 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)ExperimentalPatients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients then receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL with TGFbDNRII-transduced autologous TILs infusion on day 0.
  • Cyclophosphamide
  • NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL
  • TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes

Eligibility Criteria

        Inclusion Criteria:

          -  Solid tumors refractory to treatment that are either Stage IV or locally advanced

          -  For cohorts 1, 2 and 3 only - Patient's tumor must be positive by histological or
             molecular assay for NY-ES0-1, according to the screening algorithm under "tumor
             biopsy". Historical results may be used.

          -  For Cohort 4 - NY-ESO-1 results will be noted but NY-ESO-1 positivity not required for
             eligibility.

          -  Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping
             (blood test or buccal swab). Historical documentation acceptable.

          -  Life expectancy greater than 3 months assessed by a study physician

          -  Have been informed of other treatment options

          -  A minimum of one measurable lesion defined as:

               -  Meeting the criteria for measurable disease according to Immune-Related Response
                  Evaluation Criteria in Solid Tumors (irRECIST)

               -  For patients with skin metastases, lesions selected as non-completely biopsied
                  target lesion(s) that can be accurately measured and recorded by color
                  photography with a ruler to document the size of the target lesion(s)

          -  No restriction based on prior treatments but at least 4 weeks from prior
             immunotherapy, or prior investigational agents

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Must have adequate venous access for apheresis

          -  Women of childbearing potential and men are requested to use acceptable methods of
             birth control for the duration of the study and 6 months after; 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

          -  Leukocytes: >=3,000/mcl

          -  Absolute neutrophil count: >= 1,000/mcl

          -  Platelets: >= 100,000/mcl

          -  Total bilirubin: =< 1.5 upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):
             =< 2.5 x institutional upper limit of normal

          -  Creatinine: =< 2X ULN; if creatinine > 2X ULN

          -  Creatinine clearance: must be > 60 ml/min

          -  Must be willing and able to accept the leukapheresis procedure

          -  At screening, must have tissue available for NY-ESO-1 testing (if not previously
             performed) or be willing and able to undergo a fresh tissue biopsy.

          -  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

          -  Participant must agree to and arrange for a caregiver (age >= 18 years) available 24
             hours a day/7 days a week and arrange for lodging within 45 minute drive to Roswell
             Park and transportation for a period of time after discharge from the hospital. The
             exact amount of time will depend on the individual status as determined by the
             treating physician.

        Exclusion Criteria:

          -  Previously known hypersensitivity to any of the agents used in this study

          -  Currently receiving any other investigational agents

          -  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..EKG will be done at screening. Cardiac stress test will be done as
             clinically indicated, specific test to be chosen at the discretion of the treating
             physician

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

          -  History of inflammatory bowel disease, celiac disease, or other chronic
             gastrointestinal conditions associated with diarrhea or bleeding, or current acute
             colitis of any origin

          -  Potential requirement for systemic corticosteroids or concurrent immunosuppressive
             drugs based on prior history or received systemic steroids within the last 4 weeks
             prior to enrollment (inhaled or topical steroids at standard doses or isolated use of
             steroids as premedication for medical procedures to minimize allergic reaction (e.g.
             CT scan dye)are allowed)

          -  Known active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis
             C or cytomegalovirus (CMV)

          -  Known cases of clinically active brain metastases (brain MRI as clinically indicated);
             prior evidence of brain metastasis successfully treated with surgery or radiation
             therapy will not be exclusion for participation as long as they are deemed under
             control at the time of study enrollment

          -  Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of informed consent and compliance with the requirements of this protocol

          -  Pregnancy or breast-feeding; female patients must be surgically sterile or be
             postmenopausal for two years, or must agree to use effective contraception during the
             period of treatment and 6 months after; all female patients with reproductive
             potential must have a negative pregnancy test (serum/urine) within 48 hours from
             starting the conditioning chemotherapy

          -  Lack of availability of a patient for immunological and clinical follow-up assessment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity using Common Toxicity Criteria
Time Frame:Up to 30 days
Safety Issue:
Description:Patients will be monitored by medical histories, physical examinations, ophthalmologic exams, and blood studies to detect potential toxicities from the treatment.

Secondary Outcome Measures

Measure:Expression of the NY-ESO-1 TCR transgenic protein in peripheral blood mononuclear cells (PBMC)
Time Frame:Up to 15 years
Safety Issue:
Description:TCR and vector presence will be quantitated in PBMC samples, obtained before adoptive transfer and at weeks 1, 2, 4, 8, and 12 after transgenic cell adoptive transfer. Thereafter, sampling will be every 3 months during the first year, and then every 6 to 12 months per schedule of procedures and observations.
Measure:Replication competent retrovirus (RCR)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Tumor response (complete and partial response) as determined by RECIST 1.1
Time Frame:UP to 90 days after TCR transgenic PBMC adoptive transfer
Safety Issue:
Description:Response assessment will be performed by comparing standard computed tomography imaging scans and photographs of target lesions from baseline.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated