Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.
18 Years
75 Years
Both
Malignant Pleural Mesothelioma
Trial Information
Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.
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.
Inclusion 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 with planned third cycle of palliative chemotherapy in 21 days,
- Bone marrow function: hemoglobin = 100 g/L; white blood cell count (WBC) = 3.0 x
109/L; absolute neutrophile count (ANC) = 1.5 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 = 2 mg/dL 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,
- 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome 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.
Outcome Time Frame:
until 35 days after transfer of re-directed T cells
Safety Issue:
Yes
Principal Investigator
Christoph Renner, Prof MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Hospital Zurich, Division of Immunology
Authority:
Switzerland: Swissmedic
Study ID:
FAPME-1
NCT ID:
NCT01722149
Start Date:
April 2013
Completion Date:
October 2014
Related Keywords:
- Malignant Pleural Mesothelioma
- malignant pleural mesothelioma
- re-directed T cells
- FAP
- fibroblast activation protein
- CD8 positive T cells
- pleural effusion
- Mesothelioma
- Pleural Effusion
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