AzTrials
AzTrials

HLA-A2 Positive Cells PresentEarly Phase 1NCT02774291

Anti-NY ESO-1 mTCR Peripheral Blood Lymphocytes

A Early Phase 1 study testing Aldesleukin, Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes and Cyclophosphamide in people with HLA-A2 Positive Cells Present and Metastatic Malignant Neoplasm, run by Albert Einstein College of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 66 years
What is being tested?
Aldesleukin, Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
20 Apr 2017to 4 Aug 2020
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 66 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: Pilot Study of Adoptive Cell Transfer for the Treatment of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 Murine TCR-Gene Engineered Lymphocytes

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:

  1. 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:

  1. 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.

Being tested
Aldesleukin, Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes, Cyclophosphamide, Filgrastim, Fludarabine Phosphate
Medical subject headings
Neoplasm Metastasis, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood LymphocytesBiological

    Also called Anti-thyroglobulin mTCR-transduced Autologous PBL

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FilgrastimBiological

    Also called Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF

    Given SC

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IVPB

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02774291
Study groupRoleWhat they receive
Treatment (mTCR, aldesleukin)ExperimentalPatients 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.
Receives: Biological: Aldesleukin; Biological: Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes; Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 15 years

Secondary outcomes (2)

  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.

    Measured: 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.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2016 (estimated)
  2. Study start20 Apr 2017
  3. Primary completion1 Jul 2020
  4. Study completion4 Aug 2020

Why it stopped: 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

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02774291
Sponsor's protocol ID
2015-5254
Other IDs
NCI-2015-01781, 2015-5254, P30CA013330
Status last verified
Jul 2023
First submitted
13 May 2016
Last updated
4 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Aldesleukin, Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes and Cyclophosphamide in people with HLA-A2 Positive Cells Present and Metastatic Malignant Neoplasm, run by Albert Einstein College of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.0 (time frame: Up to 15 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02774291.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in