Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

Breast Cancer Clinical Trial

Official title: A Phase I/II Clinical Trial of Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

Status Active, not recruiting

Clinical Trial Summary

The purpose of this Phase I study is to test the safety of different doses of specially prepared immune cells (called "T cells") collected from blood. The Investigators want to find a safe dose of these modified T cells for patients who have malignant pleural disease. They want to find out what effects these T cells have on the patient and the cancer (MPD).

Phase 2 part of the study, the investigators will test the dose in combination with another drug, pembrolizumab, to see what effects the study treatment has on malignant pleural mesothelioma.

Clinical Trial Description

This is an open-label, dose-escalating, non randomized, single-center, phase I/II study of mesothelin-targeted T cells administered intrapleurally as an infusion in patients with a diagnosis (histologically or cytologically documented) of MPD from mesothelioma, lung cancer, or breast cancer. Patients receiving pembrolizumab in cohort 9 only includes patients with a diagnosis of mesothelioma. The total number of patients studied will depend on the number of dose levels tested, up to a maximum dose of 6×10^7 mesothelin-targeted T cells/kg or until the maximum tolerated dose (MTD) is reached. In Phase I of this study, we anticipate infusing a minimum of 4 and a maximum of 54 evaluable patients. The total number of enrolled patients in Phase II of this study depends on the number of observed responses and ranges from 13-21 evaluable patients, including 6 patients treated at the final dose in Phase I.

For patients who were treated and were removed from study, duplicate enrollment is permitted if it is determined the patients could receive benefit. If the patients meet all eligibility criteria, they may receive treatment in a higher dose level cohort. Patients who are re-treated with CAR T cell therapy will not be considered new accruals. Outcomes of re-treated patients will be analyzed separately.

Patients may receive palliative radiotherapy for symptom management prior to or following the CAR T cell infusion. If a patient receives palliative radiotherapy, the study PI, treating Radiation Oncologist, and treating Medical Oncologist will decide whether to proceed with the infusion. Palliative radiotherapy must be completed at least 2 days prior to the administration of cyclophosphamide.

Patients in cohort 9 and in the Phase II portion of the study will begin treatment with pembrolizumab 4 weeks (+3/-1 week window) after completing CAR T cell administration. Patients will receive 3 doses of pembrolizumab given on a recurring schedule followed by reassessment. Patients responding or deriving clinical benefit, without unacceptable toxicity, will be followed for up to 6 months after the first dose of pembrolizumab and may continue pembrolizumab. Patients who cannot receive all 6 doses of pembrolizumab at MSK will be followed and medical records including images will be obtained from the treating physician. ;

Related Conditions & MeSH terms

• Breast Cancer
• Lung Cancer
• Malignant Pleural Disease
• Mesothelioma
• Metastases
• Pleural Diseases

• NCT number: NCT02414269
• Study type: Interventional
• Source: Memorial Sloan Kettering Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2015
• Completion date: April 30, 2025