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

NCT02408016 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: 2727.00NCI-2015-003292727P30CA015704
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; WT1 Positive

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events

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

  Up to 6 months after the first T cell infusion

• 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.

  Up to 4 weeks

• 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.

  Up to 100 days after the last T cell infusion

Other Outcomes (3)

• Frequency of Transferred T Cells at Biopsied Tumor Sites Between the T Cell (Tn) and Memory T Cell (Tcm) Groups

  Up to 15 years

• Functional Capacity of Transferred Cells, Measured by Production of Intracellular Cytokines

  Up to 15 years

• Time to Progression (TTP) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and RECIST 1.1 Mesothelioma Modified

  3 months after last infusion

Study Arms (3)

Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2)

EXPERIMENTAL

Patients 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.

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)

EXPERIMENTAL

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.

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)

EXPERIMENTAL

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.

Biological: Aldesleukin; Biological: Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2); Arm I, Stage II (T lymphocytes, cyclophosphamide, IL-2); Arm II (T lymphocytes, IL-2, surgery)

Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes BIOLOGICAL

Given IV

Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2); Arm I, Stage II (T lymphocytes, cyclophosphamide, IL-2); Arm II (T lymphocytes, IL-2, surgery)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2); Arm I, Stage II (T lymphocytes, cyclophosphamide, IL-2)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I, Stage I (T lymphocytes, cyclophosphamide, IL-2); Arm I, Stage II (T lymphocytes, cyclophosphamide, IL-2); Arm II (T lymphocytes, IL-2, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Arm II (T lymphocytes, IL-2, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Mesothelioma, Malignant

Interventions

aldesleukin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Pleural Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Aude Chapuis
• Organization: FHCRC

achapuis@fredhutch.org

2066674369

Study Officials

• Sylvia Lee

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 31, 2015
• First Posted: April 3, 2015
• Study Start: May 22, 2015
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: September 13, 2021
• Results First Posted: September 13, 2021

Record last verified: 2021-08

Locations

US (1)