Malignant Pleural MesotheliomaPhase 1NCT01355965
Autologous Redirected RNA Meso-CIR T Cells
A Phase 1 study testing Autologous T cells in people with Malignant Pleural Mesothelioma, run by University of Pennsylvania at 1 site in United States.
Trial summary
To determine the safety and manufacturing feasibility of IV autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin messenger RNA (mRNA) expressing a single chain antibody variable fragment linked to the intracellular CD 3 zeta T cell receptor domain and the 4-1BB costimulatory domain. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Autologous T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to Oct 2015
- Phase
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have histologically confirmed MPM (epithelial or biphasic).
- Subjects must have completed standard first line therapy with a platinum-based double regimen and had PD or they must have chosen not to pursue primary standard of care therapy.
- ECOG performance status 0 to 1.
- Age greater than 18 years
- Life expectancy > 4 months
- At least 2 weeks since prior and no other concurrent chemotherapy, radiotherapy, or immunotherapy (e.g., interferons, tumor necrosis factor, interleukins, or monoclonal antibodies). In addition, the patient must have fully recovered from any adverse events related to these agents.
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- More than 4 weeks since prior and no other concurrent investigational agents.
- Subjects must have measurable disease as defined by accepted MPM measurement techniques (modified RECIST criteria).
- Blood coagulation parameters: PT such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT < 1.2 times the upper limit of normal.
- Subjects must have adequate venous peripheral access for apheresis. Patients must also have adequate venous access for subsequent modified CIR T-cell administration which can be done through a central venous access (e.g. port of systemic chemotherapy).
- Short-term therapy for acute conditions not specifically related to MPM is allowed if such therapy does not include any immune modulating agents.
- Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device , abstinence) during the study and for 3 months following the last dose of the study cell infusion.
- Subject must understand and sign the study-specific informed consent .
- Satisfactory organ and bone marrow function as defined by :
- Absolute neutrophil count > 1,000/µl Platelets > 100,000/µl Hematocrit > 30 % AST(SGOT)/ALT(SGPT) < 3x the institutional normal upper limit Bilirubin < 2.0 mg/dL unless secondary to malignant bile duct obstruction Creatinine < 1.5x the institutional normal upper limit
Who cannot join
- Previously treated with any investigation therapy within 1 month prior to screening.
- Sacromatoid MPM histology which does not express mesothelin
- Prior invasive malignancies unless surgically and medically cured without evidence of recurrent disease for 5 years with the exception of non-melanoma skin cancer, prostate cancer with PSA level < 1.0.
- Prior hematologic malignancy with bone marrow transplantation or immune modifying therapy within the past 4 weeks with the exception of thyroid replacement.
- Use of immunosuppressive drugs with 4 weeks prior to study entry, or anticipated use of immunosuppressive agents.
- Any clinically -significant pericardial effusion, CHF (NY Heart Association Grade II-IV ), or cardiovascular condition.
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- Any clinically -significant pleural effusion or ascites that cannot be drained with standard approaches or with pre-enrollment in dwelling drainage device placement.
- Forced vital capacity < 50% predicted, DLCO < 40% predicted.
- Underlying lung disease requiring supplemental oxygen therapy.
- Have a recognized immunodeficiency disease including cellular immunodeficiency, hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired hereditary, congenital immunodeficiency.
- Viral infections: HIV, HCV, HBV.
- Pregnant women are excluded from this study because autologous transduced T cells, breastfeeding should be discontinued if the mother is treated.
- Feasibility assessment during screening demonstrates < 30% transfection of target lymphocytes, or < 5-fold expansion in modified CIR T-cells in response to CD3/CD28 costimulation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1 Clinical Trial of Autologous Mesothelin Re-Directed T Cells Administered Intravenously in Patients With Progressive Malignant Pleural Mesothelioma
To determine the safety and manufacturing feasibility of IV autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin messenger RNA (mRNA) expressing a single chain antibody variable fragment linked to the intracellular CD 3 zeta T cell receptor domain and the 4-1BB costimulatory domain.
Read the detailed description
The purpose of this study is to test the safety of infusing the study product CIR T cells. These T cells are made using T cells obtained through apheresis and introducing the T cells to a temporary gene which will cause them to start making a new type of antibody that will attach mesothelin (this antibody is found on the surface of the cancer cells). In theory, once the modified T cells attach to mesothelin, the cells will be activated to stimulate the subject's own immune system to attack the mesothelin cells. This type of modified cell is called a T cell transduced transfected with chimeric anti-mesothelin immunoreceptor. Subjects will be enrolled serially with all subjects receiving 1xe8 to 1x1e9 modified CIR T cells every other day for 3 infusions. Each patient will be observed for 9 days for toxicity assessment prior to receiving a second cycle of modified CIR T cells every other day for 3 infusions. The preceding subject must have completed the two-cycle regimen and been observed for toxicity through day 21 before the next subject can be enrolled.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Autologous T cells
- Keywords
- completed standard first line therapy, platinum based double regimen, Progressive Disease, chosen not to pursue primary standard of care therapy
- Medical subject headings
- Mesothelioma, Malignant, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous T cellsBiological
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - One dose of cells | Experimental | Subjects receive one dose of 1x108 cells on day 0 followed by one dose of 1x109 autologous transfected anti-mesothelin CAR T cells on day 7. Receives: Biological: Autologous T cells |
| Cohort 2 - three doses of cells | Experimental | receive three doses of 1x108 cells on day 0, 2, 4 (Monday-Wednesday-Friday (MWF) of Cycle 1) followed by three doses of 1x109 T cells on day 7, 9, 11 (MWF of Cycle 2). Total target dose for Cohort 2 is 3.3x109 cells. Receives: Biological: Autologous T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Occurence of study related adverse events greater than to equal to Grade 3 events that are possibly, likely or definitely related to study treatment.
Measured: Until week 4
Secondary outcomes (1)
Clinical response Rate
Effect of CIR T cell infusion on systemic adaptive and innate immunity
Measured: through 6 months post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2011 (estimated)
- Study startMay 2011
- Primary completionJul 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 PennsylvaniaThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Haas, MD, PhD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01355965
- Sponsor's protocol ID
- UPCC 17510
- Status last verified
- Sep 2017
- First submitted
- 17 May 2011
- Last updated
- 19 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Maus MV, Haas AR, Beatty GL, Albelda SM, Levine BL, Liu X, Zhao Y, Kalos M, June CH. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2013 Jul;1(1):26-31. doi: 10.1158/2326-6066.CIR-13-0006. Epub 2013 Apr 7.
PubMed 24777247
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial of Autologous Mesothelin Re-Directed T Cells Administered Intravenously in Patients With Progressive Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT01355965
- Acronym / sponsor ID
- UPCC 17510
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- completed standard first line therapy, platinum based double regimen, Progressive Disease, chosen not to pursue primary standard of care therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 19 May 2011 (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.
To determine the safety and manufacturing feasibility of IV autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin messenger RNA (mRNA) expressing a single chain antibody variable fragment linked to the intracellular CD 3 zeta T cell receptor domain and the 4-1BB costimulatory domain.
Detailed description
The purpose of this study is to test the safety of infusing the study product CIR T cells. These T cells are made using T cells obtained through apheresis and introducing the T cells to a temporary gene which will cause them to start making a new type of antibody that will attach mesothelin (this antibody is found on the surface of the cancer cells). In theory, once the modified T cells attach to mesothelin, the cells will be activated to stimulate the subject's own immune system to attack the mesothelin cells. This type of modified cell is called a T cell transduced transfected with chimeric anti-mesothelin immunoreceptor. Subjects will be enrolled serially with all subjects receiving 1xe8 to 1x1e9 modified CIR T cells every other day for 3 infusions. Each patient will be observed for 9 days for toxicity assessment prior to receiving a second cycle of modified CIR T cells every other day for 3 infusions. The preceding subject must have completed the two-cycle regimen and been observed for toxicity through day 21 before the next subject can be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - One dose of cells | Experimental | Biological: Autologous T cellsSubjects receive one dose of 1x108 cells on day 0 followed by one dose of 1x109 autologous transfected anti-mesothelin CAR T cells on day 7. |
| Cohort 2 - three doses of cells | Experimental | Biological: Autologous T cellsreceive three doses of 1x108 cells on day 0, 2, 4 (Monday-Wednesday-Friday (MWF) of Cycle 1) followed by three doses of 1x109 T cells on day 7, 9, 11 (MWF of Cycle 2). Total target dose for Cohort 2 is 3.3x109 cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must have histologically confirmed MPM (epithelial or biphasic).
- Subjects must have completed standard first line therapy with a platinum-based double regimen and had PD or they must have chosen not to pursue primary standard of care therapy.
- ECOG performance status 0 to 1.
- Age greater than 18 years
- Life expectancy > 4 months
Key exclusion criteria (13 listed)
- Previously treated with any investigation therapy within 1 month prior to screening.
- Sacromatoid MPM histology which does not express mesothelin
- Prior invasive malignancies unless surgically and medically cured without evidence of recurrent disease for 5 years with the exception of non-melanoma skin cancer, prostate cancer with PSA level < 1.0.
- Prior hematologic malignancy with bone marrow transplantation or immune modifying therapy within the past 4 weeks with the exception of thyroid replacement.
- Use of immunosuppressive drugs with 4 weeks prior to study entry, or anticipated use of immunosuppressive agents.
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 |
|---|---|---|
| Autologous T cells | Biological | Cohort 1 - One dose of cells, Cohort 2 - three doses of cells |
Primary outcome
Adverse Events
Time frame: Until week 4
Occurence of study related adverse events greater than to equal to Grade 3 events that are possibly, likely or definitely related to study treatment.
1 secondary outcome
Clinical response Rate
Time frame: through 6 months post dosing
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 19 Sep 2017.
- Derived from this study: PubMed 24777247Maus MV, Haas AR, Beatty GL, Albelda SM, Levine BL, Liu X, Zhao Y, Kalos M, June CH. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2013 Jul;1(1):26-31. doi: 10.1158/2326-6066.CIR-13-0006. Epub 2013 Apr 7.
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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.
Andrew Haas, MD, PhD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous T cells in people with Malignant Pleural Mesothelioma, run by University of Pennsylvania at 1 site in United States.
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 15 inclusion and 13 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 19 Sep 2017. 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 United States. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Adverse Events (time frame: Until week 4). 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 NCT01355965, which also lists 1 linked publication.
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 19 Sep 2017.