Anti-NY ESO-1 mTCR Peripheral Blood Lymphocytes

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

EARLY_PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-20

Study Completion Date

2020-08-04

Brief Summary

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This pilot clinical trial studies the side effects of anti-ESO (cancer/test antigen) murine T-cell receptor (mTCR)-transduced autologous peripheral blood lymphocytes and combination chemotherapy with cyclophosphamide and fludarabine phosphate in treating patients with cancer that has spread to other places in the body (metastatic) and expresses the gene NY-ESO-1. Donor white blood cells that are treated in the laboratory with anti-cluster of differentiation (CD)3 may help treat metastatic cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Aldesleukin may stimulate white blood cells, including natural killer cells, to kill metastatic cancer cells. Giving anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes together with combination chemotherapy and aldesleukin may kill more cancer cells.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the administration of anti-ESO (cancer/test antigen) mTCR (T cell receptor)-engineered peripheral blood lymphocytes (anti-thyroglobulin mTCR-transduced autologous peripheral blood lymphocytes) plus high-dose aldesleukin following a nonmyeloablative lymphoid depleting preparative regimen in human leukocyte antigen (HLA)-A2 positive patients with metastatic cancer expressing the ESO antigen.

SECONDARY OBJECTIVES:

I. Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

II. Determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

OUTLINE:

Patients receive standard cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6 and fludarabine phosphate via intravenous piggy back (IVPB) over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim subcutaneously (SC) on days 1-4.

After completion of study treatment, patients are followed up at 6 weeks, annually for 5 years, and then periodically for 10 years thereafter.

Conditions

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HLA-A2 Positive Cells Present Metastatic Malignant Neoplasm Metastatic Malignant Neoplasm in the Brain

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (mTCR, aldesleukin)

Patients receive standard cyclophosphamide IV over 1 hour on days -7 to -6 and fludarabine phosphate via IVPB over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim SC on days 1-4.

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given IV

Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Fludarabine Phosphate

Intervention Type DRUG

Given IVPB

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Interventions

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Aldesleukin

Given IV

Intervention Type BIOLOGICAL

Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes

Given IV

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Fludarabine Phosphate

Given IVPB

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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125-L-Serine-2-133-interleukin 2 Proleukin r-serHuIL-2 Recombinant Human IL-2 Recombinant Human Interleukin-2 Anti-thyroglobulin mTCR-transduced Autologous PBL (-)-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 Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara Oforta SH T 586

Eligibility Criteria

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Inclusion Criteria

* Measurable metastatic cancer that expresses NY ESO-1 as assessed by one of the following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO
* Confirmation of diagnosis of metastatic cancer by the Laboratory of Pathology at the Montefiore Medical Center
* Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
* 3 or fewer brain metastases; Note: if lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible
* More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo); Note: patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria
* Eight weeks must have elapsed from the time of any antibody therapy that could affect an anti-cancer immune response, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) therapy, at the time the patient receives the preparative regimen to allow antibody levels to decline; Note: patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies
* Willing to sign a durable power of attorney
* Able to understand and sign the informed consent document
* Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
* Life expectancy of greater than three months
* Patients must be HLA-A\*0201 positive
* Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after cells are no longer detected in the blood
* Serology:

* Seronegative for human immunodeficiency virus (HIV) antibody; (the experimental treatment being evaluated in this protocol depends on an intact immune system; patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities)
* Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody; if hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative
* Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus
* Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim
* White blood cell (WBC) \>= 3000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \> 8.0 g/dl
* Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< to 2.5 times the upper limit of normal
* Serum creatinine =\< to 1.6 mg/dl
* Total bilirubin =\< to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl

Exclusion Criteria

* Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
* Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
* Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease
* Concurrent opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system; patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
* Concurrent systemic steroid therapy
* History of severe immediate hypersensitivity reaction to any of the agents used in this study
* History of coronary revascularization or ischemic symptoms
* History of or active central nervous system (CNS) or peripheral nerve stimulation (PNS) involvement
* Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:

* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
* Age \>= 60 years old
* Pulmonary function testing in patients with:

* A prolonged history of cigarette smoking (20 pk/yr of smoking within the past two years)
* Symptoms of respiratory dysfunction

Minimum Eligible Age

18 Years

Maximum Eligible Age

66 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No