Malignant Pleural MesotheliomaEarly Phase 1NCT01722149
Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma
A Early Phase 1 study testing Adoptive Transfer of re-directed T cells in people with Malignant Pleural Mesothelioma, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Adoptive Transfer of re-directed T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteSwitzerland
- Study dates
- 19 Feb 2015to 18 Jul 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Zurich, Division of Oncology
Zurich, Canton of Zurich, 8091
About this study
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.
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
Read the 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.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Adoptive Transfer of re-directed T cells
- Keywords
- malignant pleural mesothelioma, re-directed T cells, FAP, fibroblast activation protein, CD8 positive T cells, pleural effusion
- Medical subject headings
- Mesothelioma, Malignant, Pleural Effusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adoptive Transfer of re-directed T cellsGenetic
Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion
| Study group | Role | What they receive |
|---|---|---|
| Adoptive Transfer of re-directed T cells | Experimental | Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion Receives: Genetic: Adoptive Transfer of re-directed T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: until 35 days after transfer of re-directed T cells
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2012 (estimated)
- Study start19 Feb 2015
- Primary completion22 Mar 2019
- Study completion18 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- Adoptive Transfer of re-directed FAP-specific T cells
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alessandra Curioni, MD, Principal investigator, University Hospital Zurich, Division of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01722149
- Sponsor's protocol ID
- FAPME-1
- Status last verified
- Aug 2019
- First submitted
- 31 Oct 2012
- Last updated
- 7 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23937772Petrausch 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.
PubMed 23259649
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01722149
- Acronym / sponsor ID
- FAPME-1
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- malignant pleural mesothelioma, re-directed T cells, FAP, fibroblast activation protein, CD8 positive T cells, pleural effusion
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 19 Feb 2015 (actual)
- Primary completion
- 22 Mar 2019 (actual)
- Study completion
- 18 Jul 2019 (actual)
- First posted
- 6 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Adoptive Transfer of re-directed FAP-specific T cells
| Arm | Type | Receives |
|---|---|---|
| Adoptive Transfer of re-directed T cells | Experimental | Genetic: Adoptive Transfer of re-directed T cellsAdoptive Transfer of re-directed FAP specific T cells in the pleural effusion |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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,
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adoptive Transfer of re-directed T cellsAdoptive Transfer of 10e6 re-directed T cells in the pleural effusion | Genetic | Adoptive Transfer of re-directed T cells |
Primary outcome
Safety
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
- Background: PubMed 23937772Schuberth 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.
- Background: PubMed 23259649Petrausch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandra Curioni, MD principal investigator
University Hospital Zurich, Division of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Adoptive Transfer of re-directed T cells in people with Malignant Pleural Mesothelioma, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: until 35 days after transfer of re-directed T cells). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01722149, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.