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

NCT01722149 | Completed Early Phase 1 DMC

• 1 other identifier: FAPME-1
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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

Conditions

Malignant Pleural Mesothelioma

Keywords

malignant pleural mesothelioma; re-directed T cells; FAP; fibroblast activation protein; CD8 positive T cells; pleural effusion

Outcome Measures

Primary Outcomes (1)

• Safety

  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.

  until 35 days after transfer of re-directed T cells

Study Arms (1)

Adoptive Transfer of re-directed T cells

EXPERIMENTAL

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

Genetic: Adoptive Transfer of re-directed T cells

Interventions

Adoptive Transfer of re-directed T cells GENETIC

Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion

Adoptive Transfer of re-directed T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed and documented malignant pleural mesothelioma with pleural effusion,
• Signed Informed Consent after being informed,
• Patients medically and/or functionally at screening not accessible for surgical treatment
• Bone marrow function: hemoglobin \>/= 100 g/L; white blood cell count (WBC) \>/= 1.0 x 109/L; absolute neutrophile count (ANC) \>/= 0.5 x 109/L; platelet count \>/= 100 x 109/L,
• Hepatic: aspartate transaminase (AST) and alanine transaminase (ALT) \</= 2.5 times upper limit of normal (ULN)); bilirubin \</= 1.5 x ULN,
• Renal: creatinine = 176 umol/l and creatinine clearance = 45 mL/min,
• No concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents,
• The patient has received no major organ allograft,
• HIV-negative,
• HBV and HCV negative,
• No uncontrolled bleeding disorder,
• Patients of child-producing potential must agree to use contraception while enrolled in the study and for 24 months after the adoptive transfer.

You may not qualify if:

• Contra-indications to the class of TpP, e.g. known hypersensitivity or allergy to the investigational product,
• Contra-indications on ethical grounds,
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• Lack of safe contraception: Safe contraception is defined as follows:Female and male subjects of childbearing potential, using and willing to continue using a medically reliable method of double barrier contraception for the entire study duration and the next 2 years, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices in combination with preservatives. Or subjects who are using any other method considered sufficiently reliable by the investigator in individual cases.Subjects who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
• Known or suspected non-compliance, drug or alcohol abuse
• Pericardial effusion of more than 100 ml. Pericardial involvement assessed by CT scan
• Patients with medical history of coronary heart disease (CHD), stroke or peripheral vascular disease (PVD),
• Patients with medical history of autoimmune disease such as multiple sclerosis, lupus, rheumatoid arthritis, inflammatory bowel disease or small vessel vasculitis,
• Regular intake of immune-modulating drugs,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia or confusional state of the subject,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital Zurich, Division of Oncology

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (2)

• Schuberth PC, Hagedorn C, Jensen SM, Gulati P, van den Broek M, Mischo A, Soltermann A, Jungel A, Marroquin Belaunzaran O, Stahel R, Renner C, Petrausch U. Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells. J Transl Med. 2013 Aug 12;11:187. doi: 10.1186/1479-5876-11-187.

  PMID: 23937772 BACKGROUND

• Petrausch U, Schuberth PC, Hagedorn C, Soltermann A, Tomaszek S, Stahel R, Weder W, Renner C. Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1). BMC Cancer. 2012 Dec 22;12:615. doi: 10.1186/1471-2407-12-615.

  PMID: 23259649 BACKGROUND

MeSH Terms

Conditions

Mesothelioma, Malignant; Pleural Effusion

Condition Hierarchy (Ancestors)

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

Study Officials

• Alessandra Curioni, MD

  University Hospital Zurich, Division of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Adoptive Transfer of re-directed FAP-specific T cells

Study Record Dates

• First Submitted: October 31, 2012
• First Posted: November 6, 2012
• Study Start: February 19, 2015
• Primary Completion: March 22, 2019
• Study Completion: July 18, 2019
• Last Updated: August 7, 2019

Record last verified: 2019-08

Locations

CH (1)