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Advanced Fallopian Tube CarcinomaPhase 1/2NCT02650986

Gene-Modified T Cells With or Without Decitabine in Treating Patients With Advanced Malignancies Expressing NY-ESO-1

A Phase 1/2 study testing Cyclophosphamide, Decitabine and Laboratory Biomarker Analysis in people with Advanced Fallopian Tube Carcinoma and Advanced Malignant Solid Neoplasm, run by Roswell Park Cancer Institute 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 I/IIa trial studies the side effects and best dose of gene-modified T cells when given with or without decitabine, and to see how well they work in treating patients with malignancies expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread to other places in the body (advanced). Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Cyclophosphamide, Decitabine and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
14 Jul 2017to 14 Jul 2032
Phase
Phase 1/2
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with solid tumors as described below:
  • Inoperable or metastatic (advanced) melanoma:
  • Has received, is intolerant, or refused a CTLA-4 inhibitor (ipilimumab) or a PD-1 inhibitor (nivolumab or pembrolizumab) as monotherapy and/or a combination of ipilimumab and nivolumab
  • Has received or is intolerant of a BRAF inhibitor or the combination of BRAF and MEK inhibitors for BRAFv600 mutant melanoma and a PD-1 inhibitor as monotherapy or in combination
  • Inoperable or metastatic (advanced) ovarian, primary peritoneal or fallopian tube carcinoma:
  • Has received platinum containing chemotherapy and has platinum refractory or resistant disease that has progressed on second line therapy
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  • If platinum sensitive disease, should have received >= 2 lines of chemotherapy
  • May have received PARP inhibitors, bevacizumab or other targeted VEGF inhibitor therapy
  • Inoperable or metastatic (advanced) synovial sarcoma:
  • Should have received and progressed on >= two lines of systemic therapy
  • Subjects with other histologies:
  • Must have previously received two lines of systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been deemed either non-responders (progressive disease) or have recurred
  • For cohorts 1, 2 and 3 only: Patient's tumor must be positive by histological or molecular assay for NY-ESO-1, according to the screening algorithm; historical results may be used
  • For cohort 4, NY-ESO-1 results will be noted but NY-ESO-1 positivity is not required for eligibility
  • Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping (blood test or buccal swab, historical documentation acceptable)
  • Age >= 18 years old, (Cohort 4: Age >= 12 years old)
  • Life expectancy greater than 3 months assessed by a study physician
  • Have been informed of other treatment options
  • A minimum of one measurable lesion defined as:
  • Meeting the criteria for measurable disease according to irRECIST criteria
  • 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 but at least 4 weeks from prior immunotherapy, or prior investigational agents. Note: Patients who have suffered >grade 2 irAEs during previous checkpoint inhibitor therapy should be excluded.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Must have adequate venous access for apheresis
  • Women of childbearing potential and men must agree to use effective methods of birth control for the duration of the study and 6 months after; methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used
  • Leukocytes: >= 3,000/mcl
  • Absolute neutrophil count: >= 1,000/mcl
  • Platelets: >= 100,000/mcl
  • Total bilirubin: =< 1.5 upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x institutional upper limit of normal
  • Creatinine: =< 2 X ULN; if creatinine > 2 X ULN, creatinine clearance must be > 60 ml/min
  • Must be willing and able to accept the leukapheresis procedure
  • At screening, must have tissue available for NY-ESO-1 testing (if not previously performed) or be willing and able to undergo a fresh tissue biopsy
  • Patient must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • Participant must agree to and arrange for a caregiver (age >= 18 years old) available 24 hours a day/ 7 days a week and arrange for lodging within 45 minutes drive to Roswell Park and transportation for a period of time after discharge from the hospital; the exact amount of time will depend on the individual status as determined by the treating physician
  • ELIGIBILITY CRITERIA FOR A SECOND TRANSGENIC T CELL INFUSION
  • Subjects in whom disease control was observed after the T cell infusion may be eligible for a second transgenic T cell infusion if the subject meets the following criteria:
  • Patient attained confirmed disease control (either complete remission [CR], partial remission [PR] or stable disease [SD]) after the first transgenic T cell infusion
  • Patient still meets the eligibility criteria above
  • A second T cell infusion is discussed and the patient agrees to receive it
  • Either cryopreserved extra cells from the first T cell product is available or cryopreserved autologous peripheral blood mononuclear cell (PBMC) is available for the manufacture of a second transgenic T cell product

Who cannot join

  • Previously known hypersensitivity to any of the agents used in this study
  • Currently receiving any other investigational agents. Note: Patients who have suffered >grade 2 irAEs during previous checkpoint inhibitor therapy should be excluded.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; electrocardiogram (EKG) will be done at screening; cardiac stress test will be done as clinically indicated, the specific test to be chosen at the discretion of the treating physician.
  • History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
  • History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, which in the investigator's opinion would place the patient at an increased risk for adverse effect or current acute colitis of any origin; treated cases with no active disease are eligible
  • 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 or isolated use of steroids as premedication for medical procedures to minimize allergic reaction [e.g. computed tomography (CT) scan dye] are allowed)
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  • Known active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or cytomegalovirus (CMV)
  • Known cases of clinically active brain metastases (brain magnetic resonance imaging [MRI] as clinically indicated); 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
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of compliance with the requirements of this protocol even with caregiver support
  • 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 48 hours from starting the conditioning chemotherapy
  • Lack of availability of a patient for immunological and clinical follow-up assessment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies

This phase I/IIa trial studies the side effects and best dose of gene-modified T cells when given with or without decitabine, and to see how well they work in treating patients with malignancies expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread to other places in the body (advanced). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving gene-modified T cells with or without decitabine works better in treating patients with malignancies expressing NY-ESO-1.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and feasibility of adoptive transfer of TGFbDNRII-transduced autologous tumor infiltrating lymphocytes (autologous NY-ESO-1 TCR/dnTGFbetaRII transgenic T cells).

SECONDARY OBJECTIVES:

  1. NY-ESO-1 TCR/ dnTGFbetaRII transgenic T cell persistence by analyzing serial peripheral blood samples for the presence of T cells with the NY-ESO-1 TCR by tetramer analysis.

II. To study T cell differentiation that correlates with higher anti-tumor responses.

III. To test the hypothesis that NY-ESO-1 TCR/dnTGFbetaRII will constitute in cells more efficient in inducing tumor regression.

IV. Determine objective tumor responses by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1.

EXPLORATORY OBJECTIVE:

  1. To evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy.

OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs followed by a phase IIa study. Participants are assigned 1 to 2 cohorts.

COHORT I: Patients undergo leukapheresis on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.

COHORT II: Patients undergo leukapheresis on day -6 and receive decitabine IV over 1 hour on days -6 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.

After completion of study treatment, patients are followed up at weeks 1-4, 6, 8, and 12, at 6 and 9 months, every 6 months for 5 years, and then yearly for 10 years.

Being tested
Cyclophosphamide, Decitabine, Laboratory Biomarker Analysis, Leukapheresis, TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
Medical subject headings
Fallopian Tube Neoplasms, Melanoma, Ovarian Neoplasms, Sarcoma, Synovial

What participants receive

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

  • CyclophosphamideDrug

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

    Given IV

  • DecitabineDrug

    Also called 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • TGFbDNRII-transduced Autologous Tumor Infiltrating LymphocytesBiological

    Also called TGFbDNRII-transduced Autologous TILs

    Given IV

Study groups in NCT02650986
Study groupRoleWhat they receive
Cohort I (cyclophosphamide, TCR/dnTGFbetaRII)ExperimentalPatients undergo leukapheresis on day -6 and receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.
Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
Cohort II (decitabine, cyclophosphamide, TCR/dnTGFbetaRII)ExperimentalPatients undergo leukapheresis on day -6 and receive decitabine IV over 1 hour on days -6 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.
Receives: Drug: Cyclophosphamide; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicities

    Will be assessed using Common Toxicity Criteria. Patients will be monitored by medical histories, physical examinations, ophthalmologic exams, and blood studies to detect potential toxicities from the treatment.

    the number of patients experiencing a DLT are reported.

    Measured: Up to 30 days

  2. Number of Participants With Feasibility Concerns in Manufacturing of NY-ESO-1/ dnTGFbetaRII Engineered Cells

    Unfeasibility will be defined as 3 or more preparations not meeting the lot release criteria in each cohort. Sufficient numbers of circulating, lot released confirmed T cells will be measured prior to administration.

    The count of patients not meeting the preparation criteria are reported.

    Measured: 1 month

Secondary outcomes (3)

  1. Expression of the NY-ESO-1 T Cell Receptor (TCR) Transgenic Protein in Peripheral Blood Mononuclear Cells (PBMC)

    TCR and vector presence will be quantitated in PBMC samples, obtained before adoptive transfer and at weeks 1, 2, 4, 8, and 12 after transgenic cell adoptive transfer. Thereafter, sampling will be every 3 months during the first year, and then every 6 to 12 months per schedule of procedures and observations.

    Measured: Up to 15 years

  2. Replication Competent Retrovirus (RCR)

    Will be assessed in blood by polymerase chain reaction (PCR).

    Measured: Up to 1 year

  3. Tumor Response (Complete and Partial Response)

    Will be determined by immune-related Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response assessment will be performed by comparing standard computed tomography imaging scans and photographs of target lesions from baseline.

    Measured: Up to 90 days after TCR transgenic PBMC adoptive transfer

Timeline

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

  1. First posted8 Jan 2016 (estimated)
  2. Study start14 Jul 2017
  3. Primary completion4 Mar 2021
  4. Study completion14 Jul 2032 (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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02650986
Sponsor's protocol ID
I 258514
Other IDs
NCI-2015-02080, I 258514, P30CA016056, R01CA164333
Status last verified
Jun 2026
First submitted
21 Dec 2015
Last updated
8 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Decitabine and Laboratory Biomarker Analysis in people with Advanced Fallopian Tube Carcinoma and Advanced Malignant Solid Neoplasm, run by Roswell Park Cancer Institute 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 41 inclusion and 11 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 8 Jul 2026. 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 combined 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.

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?

Yes. Results are posted in the registry (first posted 31 May 2022). 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 Dose Limiting Toxicities (time frame: Up to 30 days). The study lists 2 primary outcomes in all. 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 NCT02650986.

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 8 Jul 2026.

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