NCT01697527

Brief Summary

This phase II trial will examine whether genetically reprogramming a patient's disease fighting white blood cells may build an immune response to kill cancer cells that express the NY-ESO-1 protein. In this study, this genetic therapy will be given during a stem cell transplant along with a vaccine therapy. The vaccine will be made using the NY-ESO-1 protein and may help to stimulate the engineered immune response to tumor cells.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_2

Timeline
19mo left

Started Nov 2012

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress90%
Nov 2012Nov 2027

First Submitted

Initial submission to the registry

September 28, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 2, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

November 2, 2012

Completed
14 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 2, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

November 2, 2027

Last Updated

November 24, 2025

Status Verified

November 1, 2025

Enrollment Period

14 years

First QC Date

September 28, 2012

Last Update Submit

November 19, 2025

Conditions

Malignant Neoplasm

Outcome Measures

Primary Outcomes (1)

  • Clinical response

    Will be determined by RECIST 1.1 Criteria on Day +90

    Day +90

Secondary Outcomes (2)

  • NY-ESO-1 TCR transgenic cell persistence, quantitated in PBMC samples

    Up to 6 years

  • NY-ESO-1 TCR transgenic cell tumor trafficking

    Up to 40 days

Study Arms (1)

Treatment (gene and vaccine therapy)

EXPERIMENTAL

CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on days -5 to -4 and fludarabine phosphate IV over 30 minutes on days -4 to -1. TRANSPLANT: Patients receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL IV on day 0. Patients also receive NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy ID on days 1, 14, and 30 and aldesleukin SC BID on days 1-14. Patients may receive 3 additional doses of NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy after day 90.

Biological: aldesleukinDrug: fludarabine phosphateDrug: cyclophosphamideOther: laboratory biomarker analysisBiological: NY-ESO-1 reactive TCR retroviral vector transduced autologous PBLBiological: dendritic cell vaccine therapyRadiation: fludeoxyglucose F 18Procedure: positron emission tomography

Interventions

aldesleukinBIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Treatment (gene and vaccine therapy)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (gene and vaccine therapy)
cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (gene and vaccine therapy)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (gene and vaccine therapy)
NY-ESO-1 reactive TCR retroviral vector transduced autologous PBLBIOLOGICAL

Undergo NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL

Also known as: anti-NY-ESO-1 TCR gene-engineered lymphocytes, anti-NY-ESO-1 TCR retroviral vector-transduced lymphocytes
Treatment (gene and vaccine therapy)
dendritic cell vaccine therapyBIOLOGICAL

Given NY-ESO-1-157-165 peptide pulsed dendritic cell vaccine ID

Treatment (gene and vaccine therapy)
fludeoxyglucose F 18RADIATION

Undergo PET scan using \[18F\] FDG tracer

Also known as: 18FDG, FDG
Treatment (gene and vaccine therapy)
positron emission tomographyPROCEDURE

Undergo fludeoxyglucose F18 PET

Also known as: FDG-PET, PET, PET scan, tomography, emission computed
Treatment (gene and vaccine therapy)

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Stage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are available.
  • At least 1 lesion amenable for an outpatient biopsy; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists. Patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion.
  • NY-ESO-1 positive malignancy by IHC utilizing commonly available NY-ESO-1 antibodies.
  • HLA-A\*0201 (HLA-A2.1) positivity by molecular subtyping.
  • Age greater than or equal to 16 years old.
  • Life expectancy greater than 3 months assessed by a study physician.
  • A minimum of one measurable lesion defined as:
  • a. Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).
  • For patients with skin metastases, lesions 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).
  • No restriction based on prior treatments.
  • ECOG performance status (PS) 0 or 1.
  • Adequate bone marrow and hepatic function determined within 30-60 days prior to enrollment, defined as:
  • Absolute neutrophil count \> or = 1.5 x 109 cells/L.
  • Platelets \> or = 100 x 109/L.
  • Hemoglobin \> or = 10 g/dL.
  • +6 more criteria

You may not qualify if:

  • Previously known hypersensitivity to any of the agents used in this study.
  • Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol. However, cell harvesting by leukapheresis may be performed before one month from prior therapy if the study investigators consider that it will not have a detrimental impact on the generation of the two cell therapies in this protocol.
  • History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin.
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed).
  • HIV seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lympho-depletion. 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.
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
  • 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 6 months after. 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 ECG abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) \< 45% on a cardiac stress test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test)
  • Similarly, patients who are 50 years old with a baseline LVEF \< 45% will be excluded.
  • Patients with ECG results of any conduction delays (PR interval \>200ms, QTC \> 480ms), sinus bradycardia (resting heart rate \<50 beats per minute), sinus tachycardia (HR\>120 beats per minute) will be evaluated by a cardiologist prior to starting the trial. Patients with any arrhythmias, including atrial fibrillation/atrila flutter, excessive ectopy (defined as \>20 PVCs per minute), ventricular tachycardia, 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 FEV1/FVC\< 70% of predicted for normality will be excluded.
  • Received 3 or more prior myelotoxic treatment regimens.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of California at Los Angeles (UCLA )

Los Angeles, California, 90095, United States

Location

Related Publications (1)

  • Nowicki TS, Berent-Maoz B, Cheung-Lau G, Huang RR, Wang X, Tsoi J, Kaplan-Lefko P, Cabrera P, Tran J, Pang J, Macabali M, Garcilazo IP, Carretero IB, Kalbasi A, Cochran AJ, Grasso CS, Hu-Lieskovan S, Chmielowski B, Comin-Anduix B, Singh A, Ribas A. A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab. Clin Cancer Res. 2019 Apr 1;25(7):2096-2108. doi: 10.1158/1078-0432.CCR-18-3496. Epub 2018 Dec 20.

    PMID: 30573690DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

aldesleukinInterleukin-2fludarabine phosphateCyclophosphamideFluorodeoxyglucose F18Magnetic Resonance Spectroscopy2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Intervention Hierarchy (Ancestors)

InterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological FactorsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsDeoxyglucoseDeoxy SugarsCarbohydratesSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Study Officials

  • Antonio Ribas, MD, PhD

    Jonsson Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 28, 2012

First Posted

October 2, 2012

Study Start

November 2, 2012

Primary Completion (Estimated)

November 2, 2026

Study Completion (Estimated)

November 2, 2027

Last Updated

November 24, 2025

Record last verified: 2025-11

Locations

US(1)