Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma

Early Phase 1

Completed

• Conditions: Malignant Pleural Mesothelioma
• Interventions: Genetic: Adoptive Transfer of re-directed T cells

• Registration Number: NCT01722149
• Lead Sponsor: University of Zurich

Brief Summary

MPM patients are not eligible for surgical procedures like decortication or pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP which serves as target structure in MPM.

* Trial with immunomodulatory product / biological

Detailed Description

This is a phase I trial for patients with malignant pleural mesothelioma. A fixed single dose of adoptively transferred FAP-specific CD8 positive re-directed T cells will be given in the pleural effusion.

Three patients who are at the time point of screening not operable will be treated with re-directed T cells administered into the pleural effusion after completion of 3 cycles of palliative chemotherapy. In the case of one AE grade III/IV or one SAE - and the occurrence of DLT both judged to be treatment related by an independent safety monitoring board - the patient number will be expanded to 6 patients. The study will be stopped if one additional DLT occurs also judged to be treatment related.

Patients will be treated with 1x10e6 re-directed FAP-specific T cells injected in the pleural effusion. The study ends 35 days after adoptive T cell transfer. Re-directed FAP-specific T cells will be administered at day 0 (day 14 of the third cycle of palliative chemotherapy). The study is designed to demonstrate safety of 1x10e6 re-directed FAP-specific T cells. The next patient will be enrolled earliest, when the previous patient completed day +14 and the safety monitoring board has not declared any DLTs. The palliative chemotherapy is not part of the study protocol.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-10-31
• Study First Submitted QC: 2012-11-02
• Study First Posted: 2012-11-06
• Study Start: 2015-02-19
• Primary Completion: 2019-03-22
• Study Completion: 2019-07-18
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-05
• Last Update Posted: 2019-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Adoptive Transfer of re-directed T cells	Adoptive Transfer of re-directed T cells	Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion

Primary Outcome Measures

Name	Time	Method
Safety	until 35 days after transfer of re-directed T cells	Incidence and severity of treatment-related laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version v4.03 criteria as grade III-IV. In the case of one AE grade III/IV or one SAE the safety monitoring board will judge whether the case is treatment related and whether it have to be counted as DLT.

Trial Locations

Locations (1)

University Hospital Zurich, Division of Oncology; 🇨🇭 Zurich, ZH, Switzerland