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

Primary Purpose

Malignant Pleural Mesothelioma

Status
Completed
Phase
Early Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Adoptive Transfer of re-directed T cells
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring malignant pleural mesothelioma, re-directed T cells, FAP, fibroblast activation protein, CD8 positive T cells, pleural effusion

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • 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.

Exclusion criteria:

  • 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.

Sites / Locations

  • University Hospital Zurich, Division of Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adoptive Transfer of re-directed T cells

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
October 31, 2012
Last Updated
August 5, 2019
Sponsor
University of Zurich
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1. Study Identification

Unique Protocol Identification Number
NCT01722149
Brief Title
Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma
Official Title
Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
February 19, 2015 (Actual)
Primary Completion Date
March 22, 2019 (Actual)
Study Completion Date
July 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
malignant pleural mesothelioma, re-directed T cells, FAP, fibroblast activation protein, CD8 positive T cells, pleural effusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Adoptive Transfer of re-directed FAP-specific T cells
Masking
None (Open Label)
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adoptive Transfer of re-directed T cells
Arm Type
Experimental
Arm Description
Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion
Intervention Type
Genetic
Intervention Name(s)
Adoptive Transfer of re-directed T cells
Intervention Description
Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion
Primary Outcome Measure Information:
Title
Safety
Description
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.
Time Frame
until 35 days after transfer of re-directed T cells

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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. Exclusion criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alessandra Curioni, MD
Organizational Affiliation
University Hospital Zurich, Division of Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Zurich, Division of Oncology
City
Zurich
State/Province
ZH
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
23937772
Citation
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.
Results Reference
background
PubMed Identifier
23259649
Citation
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.
Results Reference
background

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

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