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HLA-A*0201 Positive Cells PresentPhase 1NYESO SCTNCT03240861

Genetically Engineered PBMC and PBSC Expressing NY-ESO-1 TCR After a Myeloablative Conditioning Regimen to Treat Patients With Advanced Cancer

A Phase 1 study testing 18F-FHBG, Aldesleukin and Busulfan in people with HLA-A*0201 Positive Cells Present and Locally Advanced Malignant Neoplasm, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Terminated

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

Official record
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Trial summary

This phase I clinical trial evaluates the safety and feasibility of administering NY-ESO-1 TCR (T cell receptor)engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after a myeloablative conditioning regimen to treat patients with cancer that has spread to other parts of the… Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
18F-FHBG, Aldesleukin and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
26 Jul 2017to 19 Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Stage IV or locally advanced unresectable cancers for which no alternative therapies with proven survival advantage are available
  • NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commercially available NY-ESO-1 antibodies
  • HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping
  • Age greater than or equal to 16 years old; if patients 16-17 years old are enrolled in the trial, they will only be enrolled after 3 patients >= 18 years old have been treated, and the treatment has been shown to be safe
  • A minimum of one measurable lesion defined as:
  • Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
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  • Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Adequate bone marrow and major organ function to undergo a PBSC transplant determined within 30-60 days prior to enrollment using standard phase 1 criteria for organ function defined as:
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9 cells/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x ULN (upper limit of normal) (=< 5 x ULN, if documented liver metastases are present)
  • Total bilirubin =< 2 x ULN (except patients with documented Gilbert?s syndrome)
  • Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)
  • Must be willing and able to accept at least three leukapheresis procedures
  • Must be willing and able to undergo three research PET scans
  • Must be willing and able to provide written informed consent

Who cannot join

  • Inability to purify >= 2.5 x 10^6 CD34-enriched cells/kg of patient weight from the pooled G-CSF mobilized leukapheresis products
  • Previously known hypersensitivity to any of the agents used in this study; known sensitivity to busulfan or fludarabine
  • Received systemic treatment for cancer, including immunotherapy, within 28 days prior to initiation of conditioning chemotherapy administration within this protocol
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
  • Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
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  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • Known clinically active brain metastases; prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential brain metastases
  • Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators
  • Since IL-2 is administered following cell infusion:
  • Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia with evidence of ischemia on a cardiac stress test (stress thallium, stress multigated acquisition [MUGA], dobutamine echocardiogram or other stress test)
  • Similarly, patients with a baseline left ventricular ejection fraction (LVEF) < 45% will be excluded.
  • Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate >120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia or 3rd degree heart block will be excluded from the study unless cleared by a cardiologist
  • Patients with pulmonary function test abnormalities as evidenced by a (forced expiratory volume 1 [FEV1]/forced vital capacity [FVC ] < 70% of predicted for normality will be excluded
  • Bone marrow involvement based on PET/CT scan at screening
  • Active or recent herpes simplex virus (HSV) infection or cytomegalovirus (CMV) based on symptoms with positive swab culture and/or positive IgM (immunoglobulin M) screening
  • Liver metastases with no other metastatic sites

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a Myeloablative Conditioning Regimen, With Administration of Interleukin-2, in Patients With Advanced Malignancies

This phase I clinical trial evaluates the safety and feasibility of administering NY-ESO-1 TCR (T cell receptor)engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after a myeloablative conditioning regimen to treat patients with cancer that has spread to other parts of the body. The conditioning chemotherapy makes room in the patient?s bone marrow for new blood cells (PBMC) and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR PBMC and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety of administering the combination of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) following a reduced intensity conditioning regimen, both of which have been genetically modified to express NY-ESO-1 TCR.

SECONDARY OBJECTIVES:

  1. To determine the feasibility of delivering the combination of TCR transduced autologous PBMC and CD34+ PBSC to patients.

II. To determine the persistence of NY-ESO-1 TCR transduced PBMC and the progeny of TCR transduced PBSC in serial peripheral blood samples.

III. Objective response rate (ORR).

EXPLORATORY OBJECTIVE:

  1. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer 9-4-[18F]fluoro-3-(hydroxymethyl)butylguanine ([18F]FHBG) with the goal of determining whether the adoptively transferred NY-ESO-1 TCR transduced PBSC home to bone marrow, differentiate into T cells and expand in secondary lymphoid organs and tumor deposits.

OUTLINE:

G-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, patients undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Patients receive G-CSF subcutaneously (SC) on mobilization days 1-8 and plerixafor SC on mobilization days 4-7, during mobilization, patients will undergo mobilized leukapheresis to obtain PBSC. Patients also undergo an unmobilized leukapheresis on day -5 before infusion of cells in order to obtain PBMC.

CHEMOTHERAPY CONDITIONING REGIMEN: Patients receive busulfan intravenously (IV) on days -4 to -2 and fludarabine IV over 30 minutes on days -3 to -2.

Patients receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and after approximately 24 hours, patients receive RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, patients receive aldesleukin (interleukin-2 (IL) or IL-2) SC twice daily (BID) for up to 7 days. Patients undergo blood collection for safety and immune monitoring on days 0, 1, 3, 5, 7, 14, 30, 60, 90, and 120. Patients receive the PET tracer 18F-FHBG IV, and after 1 hour, undergo PET/computed tomography (CT) on days 25 and 120.

After completion of study treatment, patients are followed up every 2-3 months for 2 years, every 6 months for 5 years, and annually for 15 years.

Being tested
18F-FHBG, Aldesleukin, Busulfan, Cellular Therapy, Computed Tomography
Keywords
T cells, stem cells, gene therapy, NYESO, Sarcoma
Medical subject headings
Sarcoma

What participants receive

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

  • 18F-FHBGOther

    Also called Reporter Probe 18F-FHBG

    Given IV

  • AldesleukinBiological

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

    Given SC

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • Cellular TherapyBiological

    Also called Cell Therapy

    Given LV-NYESO TCR/sr39TK PBSC IV and RV-NYESO TCR PBMC IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography

    Undergo PET/CT

  • FilgrastimBiological

    Also called Filgrastim XM02, Filgrastim-sndz, G-CSF, Granix

    Given SC

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • PlerixaforDrug

    Also called AMD 3100, JM-3100, Mozobil, SDZ SID 791

    Given SC

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan

    Undergo PET/CT

Study groups in NCT03240861
Study groupRoleWhat they receive
Treatment (Genetically engineered PBMC and PBSC)ExperimentalG-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, patients undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Patients receive G-CSF SC on mobilization days 1-8 and plerixafor SC on mobilization days 4-7. Patients also undergo an unmobilized leukapheresis on day -5 before infusion of cells. CHEMOTHERAPY CONDITIONING REGIMEN: Patients receive busulfan IV on days -4 to -2 and fludarabine IV over 30 minutes on days -3 to -2. Patients receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and after approximately 24 hours, patients receive RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, patients receive aldesleukin SC BID for up to 7 days. Patients undergo blood collection for safety and immune monitoring on days 0, 1, 3, 5, 7, 14, 30, 60, 90, and 120. Patients receive 18F-FHBG IV, and after 1 hour, undergo PET/CT on days 25 and 120.
Receives: Other: 18F-FHBG; Biological: Aldesleukin; Drug: Busulfan; Biological: Cellular Therapy; Procedure: Computed Tomography; Biological: Filgrastim; Drug: Fludarabine; Procedure: Leukapheresis; Drug: Plerixafor; Procedure: Positron Emission Tomography

What is being measured

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

  1. Incidence of dose limiting toxicity

    Safety will be assessed by monitoring and recording potential adverse effects of the treatment using the Common Toxicity Criteria at each study visit. Subjects will be monitored by medical histories, physical examinations and blood studies to detect potential toxicities from the treatment. If there are no dose limiting toxicities observed, the cohort will be expanded to 12 subjects. If 1/3 are observed, up to 6 subjects will be recruited. If less than 2/6 are observed, the cohort will be expanded to a total of 12 subjects. If a dose limiting toxicity is observed in 2 or more of 6 subjects, the

    Measured: Up to 90 days

Secondary outcomes (11)

  1. Detection of replication competent retrovirus and replication competent lentivirus

    Will be assessed by polymerase chain reaction.

    Measured: Up to 12 months post cell administration

  2. Duration of overall complete response

    Will evaluate duration of overall complete response.

    Measured: From the time measurement criteria has been first met for complete response until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years

  3. Duration of overall response

    Will evaluate duration of overall response.

    Measured: From the time measurement criteria is met for complete response/partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years

  4. Persistence of transduced T cells

    Analysis will be performed using immune monitoring techniques. The number of days until the percentage of cells expressing both NYESO-

    1 TCR and CD3 drops below the baseline percentage.

    Measured: Time Frame: Up to 2 years after transgenic cell adoptive transfer

  5. Engraftment and persistence of transduced progeny T cells

    Analysis will be performed using immune monitoring techniques. The number of days until the vector copy number in the progeny T cells is undetectable.

    Measured: Time Frame: Up to 2 years after transgenic cell adoptive transfer

  6. Engraftment and persistence of transduced T cells and progeny T cells

    Analysis will be performed both using immune monitoring and molecular techniques.

    The number of days until the vector copy number in the T cells is undetectable.

    Measured: Time Frame: Up to 2 years after transgenic cell adoptive transfer

  7. Feasibility of generation NY-ESO-1 TCR transgenic T cells and NY-ESO-1 TCR/sr39TK transgenic stem cells that meet the lot release criteria

    Feasibility of manufacturing will be assessed as:

    The number of manufacturing products meeting the lot release criteria after an acceptable number of CD34+ cells have been obtained.

    Measured: Time Frame: Up to 1 month after transgenic cell adoptive transfer

  8. Immunological monitoring will consist primarily of quantifying T cells bearing surface NY-ESO-1 TCR

    Will be assessed by NY-ESO-1126-157/MHC (major histocompatibility complex) dextramer analysis. Functional assays like enzyme-linked immunosorbent assay, intracellular cytokine staining, and/or multicytokine array assays will complement the results. Immunological assays will be compared between 1) pre-infusion peripheral blood mononuclear cells and peripheral blood stem cells, 2) an aliquot of the engineered peripheral blood lymphocytes and stem cells at the time of infusion and 3) cells recovered from patients? peripheral blood after adoptive transfer.

    Measured: Up to 15 years

  9. Objective response

    Potential objective responses to this combinatorial immunotherapy will be recorded following Response Evaluation Criteria in Solid Tumors version 1.1 criteria.

    Measured: Up to 15 years

  10. Persistence of TCR gene transduced cells

    Will be assessed by semi quantitative deoxyribonucleic acid-polymerase chain reaction using primers specific for vector sequence.

    Measured: Up to 15 years

  11. Time to disease progression

    Will evaluate length of time until disease progression.

    Measured: Time from the date of cell infusion (day 0) to the date of progressive disease first documented, or death whichever occurs first, assessed 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 posted7 Aug 2017
  2. Study start26 Jul 2017
  3. Primary completion19 Oct 2023
  4. Study completion19 Oct 2023

Why it stopped: slow accrual

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
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03240861
Sponsor's protocol ID
15-000511
Other IDs
NCI-2017-00896, Ribas NYESO SCT Cancer
Acronym
NYESO SCT
Status last verified
Oct 2023
First submitted
22 Jun 2017
Last updated
1 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Nowicki TS, Deen NNA, Peters CW, Comin-Anduix B, Medina E, Puig-Saus C, Carretero IB, Kaplan-Lefko P, Macabali MH, Garcilazo IP, Chen D, Pang J, Berent-Maoz B, Haile S, Rodriguez J, Kawakami M, Kidd CK, Champhekar A, Carlucci G, Vega-Crespo A, Chmielowski B, Singh A, Federman N, Schiller GM, Larson SJ, Allen-Auerbach M, Klomhaus AM, Zack J, Baltimore D, Yang L, Kohn DB, Witte ON, Ribas A. Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny. Nat Commun. 2025 Jul 1;16(1):5599. doi: 10.1038/s41467-025-60816-z.

    PubMed 40593578

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 18F-FHBG, Aldesleukin and Busulfan in people with HLA-A*0201 Positive Cells Present and Locally Advanced Malignant Neoplasm, run by Jonsson Comprehensive Cancer Center 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 18 inclusion and 17 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 1 Nov 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?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: slow accrual). Results are not available in the source record.

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?

Incidence of dose limiting toxicity (time frame: Up to 90 days). 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 NCT03240861, which also lists 1 linked publication.

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 1 Nov 2023.

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