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

This study is currently recruiting participants.
Verified July 2017 by Roswell Park Cancer Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02650986
First Posted: January 8, 2016
Last Update Posted: July 11, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute
  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.

Condition Intervention Phase
Adult Solid Neoplasm Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 24
Actual Study Start Date: June 30, 2017
Estimated Study Completion Date: October 20, 2019
Estimated Primary Completion Date: October 20, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

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. To test the hypothesis that NY-ESO-1 TCR/dnTGFbetaRII will constitute in cells more efficient in inducing tumor regression.

IV. Determine objective tumor responses by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Solid tumors refractory to treatment that are either Stage IV or locally advanced
  • Patient's tumor must be positive by histological or molecular assay for NY-ES0-1, according to the screening algorithm under tumor biopsy
  • NY-ESO-1 positive malignancy by immunohistochemistry (IHC) or ribonucleic acid (RNA) expression
  • Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping (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 (lymphocyte [lymph] %: >= 10%)
  • Absolute neutrophil count: >= 1,500/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: =< 2.0 mg/dl
  • Creatinine clearance: > 60 ml/min for patients with creatinine levels above institutional normal
  • Must be willing and able to accept the leukapheresis procedure
  • Must be willing and able to accept at least two tumor biopsies if feasible (optional)
  • 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:

  • 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
  • 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 are allowed)
  • Known active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or cytomegalovirus (CMV)
  • Clinically active brain metastases; radiological documentation of absence of active brain metastases at screening is required for all patients; 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
  • Evidence or history of significant cardiac disease; electrocardiogram (EKG) will be done at screening; patients 55 years and older will undergo screening by a cardiac stress test (the specific test to be chosen at the discretion of the treating physician)
  • Lack of availability of a patient for immunological and clinical follow-up assessment
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02650986


Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Richard Koya         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Richard Koya, MD Roswell Park Cancer Institute
  More Information

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02650986     History of Changes
Other Study ID Numbers: 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 )
First Submitted: December 21, 2015
First Posted: January 8, 2016
Last Update Posted: July 11, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists