Overview

Anti-ESO (Cancer/Test Antigen) mTCR-transduced Autologous Peripheral Blood Lymphocytes and Combination Chemotherapy in Treating Patients With Metastatic Cancer That Expresses NY-ESO-1

Status:
Recruiting
Trial end date:
2020-05-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Early Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Albert Einstein College of Medicine
Albert Einstein College of Medicine of Yeshiva University
Collaborator:
National Cancer Institute (NCI)
Treatments:
Aldesleukin
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Lenograstim
Sargramostim
Vidarabine
Criteria
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