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Trials / Terminated

TerminatedNCT02408016

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

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

Status
Terminated
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
11 (actual)
Sponsor
Fred Hutchinson Cancer Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. 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: I. 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.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAldesleukinGiven SC
BIOLOGICALAutologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn LymphocytesGiven IV
DRUGCyclophosphamideGiven IV
OTHERLaboratory Biomarker AnalysisCorrelative studies
PROCEDURETherapeutic Conventional SurgeryUndergo surgical resection

Timeline

Start date
2015-05-22
Primary completion
2020-06-30
Completion
2020-06-30
First posted
2015-04-03
Last updated
2021-09-13
Results posted
2021-09-13

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT02408016. Inclusion in this directory is not an endorsement.