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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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 66 Years
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02774291
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Albert Einstein College of Medicine
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Ira Braunschweig
Principal Investigator Affiliation Albert Einstein College of Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

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

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.

Arms & Interventions

Arms

Experimental: 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.

Interventions

Biological: - Aldesleukin

Given IV

Biological: - Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes

Given IV

Drug: - Cyclophosphamide

Given IV

Biological: - Filgrastim

Given SC

Drug: - Fludarabine Phosphate

Given IVPB

Other: - Laboratory Biomarker Analysis

Correlative studies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Albert Einstein College of Medicine, Bronx, New York

Status

Recruiting

Address

Albert Einstein College of Medicine

Bronx, New York, 10461

Site Contact

Ira Braunschweig

[email protected]

718-920-4826