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Malignant NeoplasmPhase 2NCT01697527

Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies

A Phase 2 study testing aldesleukin, fludarabine phosphate and cyclophosphamide in people with Malignant Neoplasm, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Malignant Neoplasm
What is being tested?
aldesleukin, fludarabine phosphate and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
2 Nov 2012to 2 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 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.
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  • A minimum of one measurable lesion defined as:
  • 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.
  • Aspartate and alanine aminotransferases (AST, ALT) < or = 2.5 x ULN (< or = 5 x ULN, if documented liver metastases are present).
  • Total bilirubin < or = 2 x ULN (except patients with documented Gilbert's syndrome).
  • Creatinine < 2 mg/dl (or a glomerular filtration rate > 60 mL/min).
  • Must be willing and able to accept at least two leukapheresis procedures.
  • Must be willing and able to accept at least two tumor biopsies.
  • Must be willing and able to provide written informed consent.

Who cannot join

  • 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, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.). Patients will be eligible if prior autoimmune disease is not deemed to be active (e.x. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy). Vitiligo will not be a basis for exclusion.
  • 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.
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  • 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.
  • Clinically active brain metastases. Radiological documentation of absence of active brain metastases at screening is required for all patients. 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California at Los Angeles (UCLA )

    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) After a Nonmyeloablative Conditioning Regimen, With Administration of NY-ESO-1157-165 Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Malignancies

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate whether we can safely administer NY-ESO-1 T cell receptor transduced autologous peripheral blood mononuclear cells (PBMCs) (up to 1x10^9 cells) along with an NY-ESO-1 dendritic cell vaccine and low dose IL-2 to patients with advanced malignancies.

II. To evaluate the feasibility of delivering two patient-specific cell therapies, the NY-ESO-1 TCR transgenic peripheral blood mononuclear cell (PBMC) and NY-ESO-1 (157-165) peptide pulsed dendritic cells (DC), within a technically challenging study design that requires other significant interventions, like a lymphodepleting conditioning regimen and post-infusion of subcutaneous low dose interleukin (IL)-2 (aldesleukin).

III. To determine the rate of objective tumor responses, by Response Evaluation Criteria in Solid Tumors (RECIST) objective response criteria.

SECONDARY OBJECTIVES:

  1. To determine the persistence of NY-ESO-1 TCR-engineered cells. This will be determined by temporally analyzing peripheral blood samples for the presence of T cells with the transduced NY-ESO-1 TCR by tetramer or dextramer analysis.

II. To explore the homing and persistence of the adoptively transferred NY-ESO-1 TCR-engineered PBMC in secondary lymphoid organs and tumor deposits via positron emission tomography (PET)-based imaging using the PET tracer fluorodeoxyglucose ([18F]FDG).

OUTLINE:

CONDITIONING: Patients receive cyclophosphamide intravenously (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 TCR transduced autologous PBMC IV on day 0. Patients also receive NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy intradermally (ID) on days 1, 14, and 30 and aldesleukin subcutaneously (SC) twice daily (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.

After completion of study treatment, patients are followed up at 30, 45, 60, and 75 days; every 3 months for 2 years; every 6 months for 3 years; and annually thereafter.

Being tested
aldesleukin, fludarabine phosphate, cyclophosphamide, laboratory biomarker analysis, NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL
Medical subject headings
Neoplasms

What participants receive

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

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given SC

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • NY-ESO-1 reactive TCR retroviral vector transduced autologous PBLBiological

    Also called anti-NY-ESO-1 TCR gene-engineered lymphocytes, anti-NY-ESO-1 TCR retroviral vector-transduced lymphocytes

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

  • dendritic cell vaccine therapyBiological

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

  • fludeoxyglucose F 18Radiation

    Also called 18FDG, FDG

    Undergo PET scan using [18F] FDG tracer

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Undergo fludeoxyglucose F18 PET

Study groups in NCT01697527
Study groupRoleWhat they receive
Treatment (gene and vaccine therapy)ExperimentalCONDITIONING: 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.
Receives: Biological: aldesleukin; Drug: fludarabine phosphate; Drug: cyclophosphamide; Other: laboratory biomarker analysis; Biological: NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL; Biological: dendritic cell vaccine therapy; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography

What is being measured

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

  1. Clinical response

    Will be determined by RECIST 1.1 Criteria on Day +90

    Measured: Day +90

Secondary outcomes (2)

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

    Measured: Up to 6 years

  2. NY-ESO-1 TCR transgenic cell tumor trafficking

    Regional uptake of fludeoxyglucose F18 within metastatic tumor sites and secondary lymphoid organs will be quantified by standardized uptake values (SUV) normalized to the body weight of the patient. The numbers of T lymphocytes will be quantified.

    Measured: Up to 40 days

Timeline

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

  1. First posted2 Oct 2012 (estimated)
  2. Study start2 Nov 2012
  3. Primary completion2 Nov 2026 (estimated)
  4. Study completion2 Nov 2027 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01697527
Sponsor's protocol ID
12-000153
Other IDs
NCI-2012-01548
Status last verified
Nov 2025
First submitted
28 Sep 2012
Last updated
24 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30573690

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing aldesleukin, fludarabine phosphate and cyclophosphamide in people with 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 21 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 24 Nov 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Clinical response (time frame: Day +90). 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 NCT01697527, 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 24 Nov 2025.

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