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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02650986
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : January 10, 2020
National Cancer Institute (NCI)
United States Department of Defense
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE December 21, 2015
First Posted Date  ICMJE January 8, 2016
Last Update Posted Date January 10, 2020
Actual Study Start Date  ICMJE June 30, 2017
Estimated Primary Completion Date August 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2016)
  • Dose-limiting toxicity using Common Toxicity Criteria [ Time Frame: Up to 30 days ]
    Patients will be monitored by medical histories, physical examinations, ophthalmologic exams, and blood studies to detect potential toxicities from the treatment.
  • Feasibility based on potential problems in the manufacturing of NY-ESO-1/ dnTGFβRII engineered cells [ Time Frame: 1 month ]
    Sufficient numbers of circulating, lot released confirmed T cells will be measured prior to administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02650986 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2016)
  • Expression of the NY-ESO-1 TCR transgenic protein in peripheral blood mononuclear cells (PBMC) [ Time Frame: Up to 15 years ]
    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.
  • Replication competent retrovirus (RCR) [ Time Frame: Up to 1 year ]
  • Tumor response (complete and partial response) as determined by RECIST 1.1 [ Time Frame: UP to 90 days after TCR transgenic PBMC adoptive transfer ]
    Response assessment will be performed by comparing standard computed tomography imaging scans and photographs of target lesions from baseline.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Gene-Modified T Cells in Treating Patients With Locally Advanced or Stage IV Solid Tumors Expressing NY-ES0-1
Official Title  ICMJE A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies
Brief Summary 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


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.


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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Solid Neoplasm
Intervention  ICMJE
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-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- 138719
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL
    Given IV
    Other Name: Anti-NY-ESO-1 TCR Retroviral Vector Transduced Autologous PBL
  • Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
    Given IV
    Other Name: TGFbDNRII-transduced Autologous TILs
Study Arms  ICMJE Experimental: Treatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)
Patients 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.
  • Drug: Cyclophosphamide
  • Other: Laboratory Biomarker Analysis
  • Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL
  • Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 6, 2016)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 20, 2022
Estimated Primary Completion Date August 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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,which in the investigator's opinion would place the patient at an increased risk for adverse effect or current acute colitis of any origin. Treated cases with no active disease are eligible.
  • 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 even with caregiver support
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02650986
Other Study ID Numbers  ICMJE I 258514
NCI-2015-02080 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 258514 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • United States Department of Defense
Investigators  ICMJE
Principal Investigator: Richard Koya, MD Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date January 2020

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