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TerminatedNCT02774291Updated Aug 4, 2023Results posted

Anti-NY ESO-1 mTCR Peripheral Blood Lymphocytes

An Early Phase 1 interventional study of Aldesleukin and Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes in HLA-A2 Positive Cells Present, Metastatic Malignant Neoplasm and Metastatic Malignant Neoplasm in the Brain, sponsored by Albert Einstein College of Medicine. Terminated at 1 site in United States. Open to participants aged 18 Years to 66 Years. Per ClinicalTrials.gov, last updated 2023-08-04.

Sponsored by Albert Einstein College of Medicine · Early Phase 1, Interventional, and Treatment

Why this study was terminated
Due to lack of accrual the study was formally terminated on 01-JUL-2020. Primary Completion and Study Completion Dates have been revised based accordingly based on respective definitions
Phase
Early Phase 1
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years to 66 Years
Sex
All
01

Study 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.

Read the detailed description

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.

02

Conditions studied

  • HLA-A2 Positive Cells Present
  • Metastatic Malignant Neoplasm
  • Metastatic Malignant Neoplasm in the Brain
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,486 are open to participants now.

This study's enrollment of 3 is below the median of 50 across 7,250 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Albert Einstein College of Medicine is the lead sponsor of 199 studies on the registry; 21 are open to participants now.

Of its 44 completed or terminated interventional studies of FDA-regulated products, 35 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 66 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study 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.

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

Interventions

  • BiologicalAldesleukin

    Given IV

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

  • BiologicalAnti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes

    Given IV

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

  • DrugCyclophosphamide

    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

  • BiologicalFilgrastim

    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

  • DrugFludarabine Phosphate

    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

  • OtherLaboratory Biomarker Analysis

    Correlative studies

06

What researchers measure

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.

    Time frame: Up to 15 years

Secondary outcomes

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

    TCR and vector presence will be quantitated in PBMC samples (5-10mL) using established PCR techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells. In addition, measurement of CD4+ and CD8+ T-cells will be conducted and studies of these T-cell subsets in the circulation will be determined by using specific PCR assays capable of detecting the unique DNA sequence for each retroviral vector engineered T-cell. Descriptive statistics will be used to determine the in vivo survival of TCR gene-engineered cells.

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

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

    Objective Response Rate will be graded based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study Descriptive statistics will be used to determine the objective response rate.

    Time frame: Up to 15 years

07

Results

Posted Aug 4, 2023

Participant flow

Participant flow — Overall Study
MilestoneTreatment (mTCR, Aldesleukin)
Started3
Completed2
Not completed1
Withdrew: Lost to follow-up1

Outcome measures

PrimaryNumber 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.

Time frame:
Up to 15 years
Reported as:
Count of participants · Participants
Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.0
ParticipantsTreatment (mTCR, Aldesleukin)
Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.02
SecondaryNumber of Participants Demonstrating in Vivo Survival of TCR Gene-engineered Cells

TCR and vector presence will be quantitated in PBMC samples (5-10mL) using established PCR techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells. In addition, measurement of CD4+ and CD8+ T-cells will be conducted and studies of these T-cell subsets in the circulation will be determined by using specific PCR assays capable of detecting the unique DNA sequence for each retroviral vector engineered T-cell. Descriptive statistics will be used to determine the in vivo survival of TCR gene-engineered cells.

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

No measurements were reported for this outcome.

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

Objective Response Rate will be graded based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study Descriptive statistics will be used to determine the objective response rate.

Time frame:
Up to 15 years

No measurements were reported for this outcome.

Adverse events

Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (mTCR, Aldesleukin)2/3 (66.7%)0/3 (0%)2/3 (66.7%)
Most frequent other events
Showing 10 of 37
Most frequent other events
EventTreatment (mTCR, Aldesleukin)
HeadacheNervous system disorders2/3
Weight GainInvestigations2/3
VomitingGastrointestinal disorders2/3
ChillsGeneral disorders2/3
HypotensionVascular disorders2/3
Neutrophil Count DecreasedInvestigations2/3
Edema limbsGeneral disorders1/3
DiarrheaGastrointestinal disorders1/3
NauseaGastrointestinal disorders1/3
ErythemaSkin and subcutaneous tissue disorders1/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (mTCR, Aldesleukin)
<=18 years0
Between 18 and 65 years3
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (mTCR, Aldesleukin)
Female1
Male2
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (mTCR, Aldesleukin)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White3
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • Albert Einstein College of Medicine
    Bronx, New York 10461, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Nov 30, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 4, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02774291
Lead sponsor
Albert Einstein College of Medicine
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
May 17, 2016
Start date
Apr 20, 2017
Primary completion
Jul 1, 2020
Completion
Aug 4, 2020
Results posted
Aug 4, 2023
Last update
Aug 4, 2023

Study contacts

Ira Braunschweig
principal investigator · Albert Einstein College of Medicine

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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