Anti-NY ESO-1 mTCR Peripheral Blood Lymphocytes

NCT02774291 | Terminated Early Phase 1 Results DMC FDA Drug

• 3 other identifiers: 2015-5254NCI-2015-01781P30CA013330
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.0

  Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.

  Up to 15 years

Secondary Outcomes (2)

• Number of Participants Demonstrating in Vivo Survival of TCR Gene-engineered Cells

  6 weeks post evaluations scan and at 3, 6, and 12 months and annually thereafter

• Number of Participants Demonstrating Objective Response Rate (Complete Response + Partial Response) Using RECIST Criteria

  Up to 15 years

Study Arms (1)

Treatment (mTCR, aldesleukin)

EXPERIMENTAL

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.

Biological: Aldesleukin; Biological: Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes; Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis

Interventions

Aldesleukin BIOLOGICAL

Given IV

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (mTCR, aldesleukin)

Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes BIOLOGICAL

Given IV

Also known as: Anti-thyroglobulin mTCR-transduced Autologous PBL

Treatment (mTCR, aldesleukin)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (mTCR, aldesleukin)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim

Treatment (mTCR, aldesleukin)

Fludarabine Phosphate DRUG

Given IVPB

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Oforta, SH T 586

Treatment (mTCR, aldesleukin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (mTCR, aldesleukin)

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Brain Neoplasms

Interventions

aldesleukin; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Braunschweig, Ira
• Organization: Albert Einstein College of Medicine/Montefiore medical center

ibraunsc@montefiore.org

718-798-7474

Study Officials

• Ira Braunschweig

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 17, 2016
• Study Start: April 20, 2017
• Primary Completion: July 1, 2020
• Study Completion: August 4, 2020
• Last Updated: August 4, 2023
• Results First Posted: August 4, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)