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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• iCasp9M28z T cell infusions — GENETIC
  Administration through the pleural catheter- On day 0 patients will be treated with genetically modified T cells. Thirty to 60 minutes before T cell infusion, patients will be given 650 mg of acetaminophen orally and 25- 50 mg of diphenhydramine orally or intravenously, to prevent infusion-related reactions. The genetically modified T cells will be infused for at least 15 minutes and no more than 2 hours through the indwelling pleural catheter depending on the volume of the T cells. A physician will be available during the infusion. Please note, during formulation of iCasp9M28z T cells, under or over estimation of CAR modified T Cells may occur. Patient may receive an altered fractionation of the total dose or up to 35% over or under total cell dose with approval of the PI. Patients who do not have enough cells to match the current dose cohort will be treated in the cohort in which they have cells available
• cyclophosphamide — DRUG
  Patients will receive cyclophosphamide intravenously (at 1.5 g/m\^2)
• pembrolizumab — DRUG
  Pembrolizumab will be given as 200 mg flat dose infusion intravenously.

Study Details

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.

Key Dates

Start date

May 31, 2015

Status verified

Oct 2025

Primary completion

Apr 30, 2026

Completion

Apr 30, 2026

Study Design

Enrollment

113 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: modified T cells alone (without chemotherapy)
  Following enrollment, leukapheresis product will be obtained in the blood donor facility at MSKCC and cryopreserved in the Cell Therapy and Cell Engineering Facility (CTCEF). Before protocol treatment, the leukapheresis product will be thawed, and T cell isolation, transduction, and expansion of iCasp928z T cells will be performed in the MSKCC CTCEF Facility. It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment.
• Experimental: modified T cells with cyclophosphamide
  Patients will receive cyclophosphamide intravenously (at 1.5 g/m\^2) , 2 - 7 (Day (-7) -(-2) days before T cell infusion. On Day 1 , patients will be admitted to the MSKCC Inpatient Service (if not already inpatients) for intravenous hydration, clinical monitoring, and blood work for immune monitoring. Standard MSKCC antiemetic therapy will be administered prior to chemotherapy to prevent nausea/vomiting. Administration of corticosteroids will be avoided as steroids may impede the efficacy of CAR T cells.
• Experimental: CAR T cell and pembrolizumab
  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. Those responding or deriving clinical benefit, without unacceptable toxicity, will continue pembrolizumab. Patients will be followed weekly for the first four weeks. Patients in cohorts 9 and in Phase II will receive pembrolizumab 4 weeks(+3/- 1 week window) following CAR T cell administration.

Primary Outcome Measure

Composite measure of severity and number of adverse events (AEs); changes in (clinical laboratory test findings (hematologic and chemistry); and physical examination. (Phase I) [ Time Frame: 1 year ]

Locations (6)

Find similar trials in Basking Ridge, NJ

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