AzTrials
AzTrials

Advanced Pleural Malignant MesotheliomaPhase 1/2NCT02408016

Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

A Phase 1/2 study testing Aldesleukin, Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes and Cyclophosphamide in people with Advanced Pleural Malignant Mesothelioma and HLA-A*0201 Positive Cells Present, run by Fred Hutchinson 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
Search all trials

Trial summary

This phase I/II trial studies the side effects and best dose of genetically modified T cells in treating patients with stage III-IV non-small cell lung cancer (NSCLC) or mesothelioma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
22 May 2015to 30 Jun 2020
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ELIGIBILITY FOR ENROLLMENT/SCREENING (ARMS 1 AND 2): Histopathological documentation of NSCLC or mesothelioma
  • ELIGIBILITY FOR ENROLLMENT/SCREENING (ARMS 1 AND 2): Patients must be able to give informed consent
  • ELIGIBILITY FOR ENROLLMENT/SCREENING (ARMS 1 AND 2): Patients must be able to provide blood and tumor samples and undergo the procedures required for this protocol
  • Arm 2 ONLY: Surgically operable NSCLC or mesothelioma
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Patients must express human leukocyte antigen (HLA)-A*0201
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Evidence of WT1 tumor expression
Show all 14Show fewer
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Patients must have received at least one line of therapy for NSCLC or mesothelioma or previously documented to have declined therapy
  • ELIGIBILITY FOR TREATMENT ON ARM 1: NSCLC patients with a mutation in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) must have demonstrated progression or intolerance to at least one of the corresponding targeted therapies (for example erlotinib or crizotinib)
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Bi-dimensionally measurable disease by palpation, clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan, positron emission tomography [PET] scan, magnetic resonance imaging [MRI], or ultrasound)
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Ninety days must have passed since the last doses of radiation or chemoradiation treatment involving lung tissue or thorax prior to T cell infusion (to avoid confounding pneumonitis)
  • ELIGIBILITY FOR TREATMENT ON ARM 1: Patients treated with prior immunotherapy including and not limited to vaccines, cytokines, T cell stimulating agents, cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors and programmed death (PD)-1 check point inhibitors are allowed on therapy provided they did not have any severe grade 4 toxicities due to prior therapy and any toxicities due to prior therapy should have resolved, if resolvable to less than or equal to grade 1
  • ELIGIBILITY FOR TREATMENT ON ARM 2: Patients must express HLA-A*0201
  • ELIGIBILITY FOR TREATMENT ON ARM 2: Evidence of WT1 tumor expression
  • ELIGIBILITY FOR TREATMENT ON ARM 2: Ninety days must have passed since the last definitive doses of radiation or chemoradiation treatment prior to T cell infusion (to avoid confounding pneumonitis)

Who cannot join

  • Eastern Cooperative Oncology Group (ECOG) performance status >= 2
  • Active autoimmune disease (e.g., systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) in which possible progression during treatment would be considered unacceptable by the investigators
  • Any condition or organ toxicity deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol
  • Men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative urine pregnancy test within 2 weeks prior to first infusion
  • Pregnant women and nursing mothers will be eligible for screening only to test HLA type by saliva or buccal swab and WT1 expression from previously collected tissue sample
  • Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation
Show all 26Show fewer
  • Exclusions for the leukapheresis procedure (this can be performed at a later time of symptoms resolve):
  • Infection, with or without antibiotic treatment
  • Recent hepatitis exposure (hepatitis B or C antigenemia)
  • Pregnancy or nursing
  • HIV or human T-lymphotropic virus (HTLV) infection
  • Positive result on standard test for syphilis (STS)
  • Unable to generate antigen-specific WT1-specific CD8+ T cells for infusions; however, the patient will have the option to receive WT1-specific T-cells if a lower than planned number of cells is available
  • Documented infections or known oral temperature > 38.2 degrees Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance; the start of treatment may be delayed
  • Systemic steroids should be stopped 2 weeks before the start of treatment; topical and inhaled steroids are allowed
  • Untreated central nervous system (CNS) metastasis that are > 1 cm or symptomatic are not allowed; (patients with CNS metastases > 1 cm or symptomatic that have been treated and demonstrated to be radiologically and clinically stable for at least 4 weeks are allowed)
  • White blood cells (WBC) < 2,000/ul
  • Hemoglobin (Hb) < 8 g/dL
  • Absolute neutrophil count (ANC) < 1,000/ul
  • Platelets < 50,000/ul
  • New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease (CAD), congestive heart failure, clinically significant hypotension or history of an ejection fraction of =< 30% (echocardiogram or multi-gated acquisition scan [MUGA])
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in 1 second (FEV1) < 2.0 L or diffusion capacity of the lungs for carbon monoxide (DLCO) (corrected for Hb) < 50% will be excluded
  • Creatinine > 1.5 x the upper limit of normal
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 5 x upper limits of normal (ULN)
  • Bilirubin > 3 x ULN that cannot be attributed to NSCLC metastasis
  • HIV or HTLV infection

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Phase I/II Study in WT1-Expressing Non-small Cell Lung Cancer and Mesothelioma, Comparing Cellular Adoptive Immunotherapy With Polyclonal Autologous Central Memory to Naïve CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T-Cell Receptor

This phase I/II trial studies the side effects and best dose of genetically modified T cells in treating patients with stage III-IV non-small cell lung cancer (NSCLC) or mesothelioma. Many types of cancer cells, including NSCLC and mesothelioma, but not most normal cells, have a protein called Wilms tumor (WT)1 on their surfaces. This study takes a type of immune cell from patients, called T cells, and modifies their genes in the laboratory so that they are programmed to find cells with WT1 and kill them. The T cells are then given back to the patient. Cyclophosphamide and aldesleukin may also stimulate the immune system to attack cancer cells. Giving cyclophosphamide and aldesleukin with laboratory-treated T cells may help the body build an immune response to kill tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety, and potential toxicities associated with treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive cluster of differentiation (CD)8+ T cells that have been transduced to express a WT1-specific T-cell receptor (TCR) (Arm 1 and Arm 2).

II. Determine the feasibility of treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive CD8+ T cells that have been transduced to express a WT1-specific TCR (Arm 1 and Arm 2).

III. Determine and compare the in vivo persistence in blood and tumor of transferred polyclonal autologous central memory and naive CD8+ T cells that have been transduced to express a WT1-specific TCR (Arm 1 and Arm 2).

EXPLORATORY OBJECTIVES:

  1. Determine the antitumor efficacy for patients with metastatic NSCLC and mesothelioma (Arm 1), as measured by time to progression (TTP) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

II. Determine the in vivo functional capacity of adoptively transferred polyclonal autologous CD8+ T cells that have been transduced to express a WT1-specific TCR, and assess the acquisition of phenotypic characteristics associated with T cell exhaustion (Arm 1 and Arm 2).

III. Determine the migration to tumor sites of adoptively transferred polyclonal autologous CD8+ T cells that have been transduced to express a WT1-specific TCR (Arm 2).

IV. Evaluate the tumor response and T cell infiltration in tumors of patients with stage IIIA NSCLC treated in the neo-adjuvant setting.

OUTLINE: This is a phase I, dose-escalation study of autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes followed by a phase II study. Patients are assigned to 1 of 3 treatment arms.

ARM I, STAGE I: Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes intravenously (IV) on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin (IL-2) subcutaneously (SC) twice daily (BID) for 14 days. Patients who have received radiation to the chest/lung tissue may receive T lymphocytes 90 days after completion of radiation.

ARM I, STAGE II: Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days.

ARM II: Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion.

After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually for 14 years.

Being tested
Aldesleukin, Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes, Cyclophosphamide, Laboratory Biomarker Analysis, Therapeutic Conventional Surgery
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Mesothelioma, Malignant

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 SC

  • Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn LymphocytesBiological

    Given IV

  • CyclophosphamideDrug

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

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgical resection

Study groups in NCT02408016
Study groupRoleWhat they receive
Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2)ExperimentalPatients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation.
Receives: Biological: Aldesleukin; Biological: Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis
Arm I, Stage II (T lymphocytes, cyclophosphamide, IL-2)ExperimentalPatients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days.
Receives: Biological: Aldesleukin; Biological: Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis
Arm II (T lymphocytes, IL-2, surgery)ExperimentalPatients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion.
Receives: Biological: Aldesleukin; Biological: Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Number of Participants With Adverse Events

    Based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

    Measured: Up to 6 months after the first T cell infusion

  2. Count of Patients for Which T Cells Are Successfully Generated and Infused and Whether Only TN or TCM Could be Generated

    There were products generated for 11 participants and 10 participants were treated on the study. 8 participants received an infusion with Tn and Tcm cells. 1 participant received infusions with only Tn cells. 1 participant received their last infusion with only Tcm cells. The one participant that was not treated did successfully have Tn and Tcm cells generated but they were not treated due to their condition worsening.

    Measured: Up to 4 weeks

  3. Persistence of Transduced T Cells

    In vivo persistence of cells generated from the TN subset with cells generated from the TCM subset will be directly compared within each patient by high throughput T-cell receptor (TCR) beta sequencing. The one-sample T test will be used to assess the difference in mean persistence between groups, in which the outcome for each patient is the time to disappearance of infused cytotoxic T lymphocytes.

    Measured: Up to 100 days after the last T cell infusion

Timeline

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

  1. First posted3 Apr 2015 (estimated)
  2. Study start22 May 2015
  3. Primary completion30 Jun 2020
  4. Study completion30 Jun 2020

Why it stopped: Terminated due to loss of funding

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
Parallel groups
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02408016
Sponsor's protocol ID
2727.00
Other IDs
NCI-2015-00329, 2727, 2727.00, P30CA015704
Status last verified
Aug 2021
First submitted
31 Mar 2015
Last updated
13 Sep 2021
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 Aldesleukin, Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes and Cyclophosphamide in people with Advanced Pleural Malignant Mesothelioma and HLA-A*0201 Positive Cells Present, run by Fred Hutchinson 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 14 inclusion and 26 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 13 Sep 2021. 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 13 Sep 2021). 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 Adverse Events (time frame: Up to 6 months after the first T cell infusion). The study lists 3 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 NCT02408016.

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 13 Sep 2021; AzTrials last refreshed its copy on 26 Oct 2026.

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

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in