MesotheliomaPhase 1MesoCancerVaNCT02395679
Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients
A Phase 1 study testing MesoCancerVac in people with Mesothelioma, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
Malignant mesothelioma is an aggressive pleural disease, related to asbestos exposure. At present, cytotoxic chemotherapy is the only evidence based treatment for the disease, but efficacy is limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma
- What is being tested?
- MesoCancerVac
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2015to Dec 2016
- 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
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients with histological or cytological confirmed diagnosed ,malignant mesothelioma, who are non progressive after at least 4 cycles of cisplatin and pemetrexed containing chemotherapy (as determined by CT scanning).
- Measurable disease on CT scanning in two dimensions by a radiologic imaging study.
- Patients must be at least 18 years old and must be able to give written informed consent.
- Patients must be ambulatory (WHO performance status 0,1, or 2 [Appendix E\&F]) The expected survival must be at least 3 months.
- Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count > 1.0 x 10e9/l, platelet count > 100 x 10e9/l, and Hb > 6.0 mmol/l.(as determined during screening
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- Positive delayed type hypersensitivity skin test (induration > 2mm after 48 hrs) against at least one positive control antigen tetanus toxoid.
- Ability to return to the Erasmus Medical Center for adequate follow-up as required by this protocol.
- Written informed consent according to good clinical practice
- Planned start date of vaccination between 5 weeks after the last dosage of chemotherapy
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Medical or psychological impediment to probable compliance with the protocol.
- Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from that 6 weeks interval
- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for five years.
- Serious concomitant disease, or active infections.
- History of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV and viral hepatitis.
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- Serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for investigational DC treatment.
- Known allergy to shell fish (may contain KLH).
- Pregnant or lactating women.
- Inadequate peripheral vein access to perform leukapheresis
- Concomitant participation in another clinical trial
- An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.
- Absence of assurance of compliance with the protocol. Lack of availability for follow-up assessment.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC, Dept. of Pulmonary Medicine
Rotterdam, South Holland, 3015GD
Cor P. van der Leest, PhD, +31 10 703 4862, k.vanderleest@erasmusmc.nl
Robin Cornelissen, PhD, +31 10 703 4862, r.cornelissen@erasmusmc.nl
About this study
Official title: A Phase I Study on Dendritic Cells Loaded With Allogeneous Cell Lysate in Patients With Mesothelioma as Maintenance Treatment After Chemotherapy
Malignant mesothelioma is an aggressive pleural disease, related to asbestos exposure. At present, cytotoxic chemotherapy is the only evidence based treatment for the disease, but efficacy is limited. The investigators have shown both in a murine model, as for the first time in patients, that dendritic cell-based immunotherapy induces tumor specific T-cell responses. However the quality and quantity of the autologous tumor cell lysate to load the dendritic cells was a major impediment for these trials. The investigators have now developed a clinical grade allogeneic tumor cell lysate which can be used to load dendritic cells of patients.
Read the detailed description
Objective: To investigate the safety of an allogeneic tumor cell lysate (PheraLys) loaded onto autologous dendritic cells (MesoCancerVac) in patients with malignant mesothelioma (MM).
Study design: A phase I study with a classical 3*3 design. Study population: Adult patients with malignant mesothelioma who were treated with chemotherapy as standard treatment.
Intervention: After chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using specific cytokines. Pulsed autologous DCs (MesoCancerVac) are re-injected 3 times every two weeks. After the third injection with MesoCancerVac, revaccinations to boost the immune system are given after 3 and 6 months.
Main study parameters/endpoints: The aim of this phase I protocol is to study the toxicity and safety of MesoCancerVac (DC-based immunotherapy) in MM patients. Toxicities will be scored according to common toxicity criteria version 4.0. The following toxicities occurring during 8 weeks after the first vaccination, will be considered as dose-limiting toxicities (DLTs).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients have to undergo extra outdoor visits for this study (10-20) and extra invasive procedures especially for this trial, like a catheter in a blood vessel. These are invasive procedure but risks are limited. This iv entrance is necessary every time, for the leukopheresis, for blood samples and for the injection of the dendritic cells. A leucopheresis is a standard procedure and will be performed according to guidelines. There is a limited risk for transient thrombocytopenia and leukopenia.
The administration of autologous cells, that have been loaded with allogeneic human materials, is a potential risk and that is the subject of the study. Because not the lysate itself is administered to the patients but only when it is processed by the dendritic cells of the patient the investigators expect these risks to be limited.
- Conditions
- Mesothelioma
- Being tested
- MesoCancerVac
- Keywords
- Dendritic cell-based immunotherapy
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesoCancerVacBiological
A leukapheresis is performed of which the monocytes are used for differentiation to DCs using specific cytokines. Pulsed autologous DCs (MesoCancerVac) are re-injected 3 times every two weeks. After the third injection with MesoCancerVac, revaccinations to boost the immune system are given after 3 and 6 months.
| Study group | Role | What they receive |
|---|---|---|
| MesoCancerVac | Experimental | Autologous dendritic cells loaded with a mixture of 5 allogenic mesothelioma tumor cell lysates 3 to 5 vaccinations with 10x10e6, 25x10e6 or 50x10e6 loaded dendritic cells i.d. and i.v. administration every two weeks Receives: Biological: MesoCancerVac |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma
Tolerability of MesoCancerVac is monitored by performing clinical laboratory tests (autoimmune responses), assessments of vital signs, full clinical examination, occurrence of adverse events.
Measured: 4 weeks after third administration
Secondary outcomes (1)
The secondary objective is the evaluation of an immune response after MesoCancerVac
Immune response is evaluated by measuring :
The functionality of T-cells by laboratory testing (cytotoxicity and interferon-gamma secretion)
Measured: 2 months after third administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2015 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, joost hegmans, Erasmus Medical Center
- Investigators
- Henk C Hoogsteden, MD PhD, Study director, Erasmus Medical Center Cancer Institure
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395679
- Sponsor's protocol ID
- NL44330.000.14
- Acronym
- MesoCancerVa
- Status last verified
- Mar 2015
- First submitted
- 30 Jan 2015
- Last updated
- 23 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90. doi: 10.1164/rccm.200909-1465OC. Epub 2010 Feb 18.
PubMed 20167848Cornelissen R, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. New roads open up for implementing immunotherapy in mesothelioma. Clin Dev Immunol. 2012;2012:927240. doi: 10.1155/2012/927240. Epub 2012 Jun 24.
PubMed 22778767Cornelissen R, Lievense LA, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Dendritic cell-based immunotherapy in mesothelioma. Immunotherapy. 2012 Oct;4(10):1011-22. doi: 10.2217/imt.12.108.
PubMed 23148753Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. doi: 10.1164/rccm.200501-057OC. Epub 2005 Mar 11.
PubMed 15764728van Gulijk M, Belderbos B, Dumoulin D, Cornelissen R, Bezemer K, Klaase L, Dammeijer F, Aerts J. Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma. Int J Cancer. 2023 Apr 1;152(7):1438-1443. doi: 10.1002/ijc.34293. Epub 2022 Oct 3.
PubMed 36104949Vroman H, Balzaretti G, Belderbos RA, Klarenbeek PL, van Nimwegen M, Bezemer K, Cornelissen R, Niewold ITG, van Schaik BD, van Kampen AH, Aerts JGJV, de Vries N, Hendriks RW. T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma. J Immunother Cancer. 2020 Mar;8(1):e000251. doi: 10.1136/jitc-2019-000251.
PubMed 32234848
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study on Dendritic Cells Loaded With Allogeneous Cell Lysate in Patients With Mesothelioma as Maintenance Treatment After Chemotherapy
- ClinicalTrials.gov ID
- NCT02395679
- Acronym / sponsor ID
- MesoCancerVa / NL44330.000.14
- Conditions
- Mesothelioma
- Keywords
- Dendritic cell-based immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 23 Mar 2015 (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.
Malignant mesothelioma is an aggressive pleural disease, related to asbestos exposure. At present, cytotoxic chemotherapy is the only evidence based treatment for the disease, but efficacy is limited. The investigators have shown both in a murine model, as for the first time in patients, that dendritic cell-based immunotherapy induces tumor specific T-cell responses. However the quality and quantity of the autologous tumor cell lysate to load the dendritic cells was a major impediment for these trials. The investigators have now developed a clinical grade allogeneic tumor cell lysate which can be used to load dendritic cells of patients.
Detailed description
Objective: To investigate the safety of an allogeneic tumor cell lysate (PheraLys) loaded onto autologous dendritic cells (MesoCancerVac) in patients with malignant mesothelioma (MM).
Study design: A phase I study with a classical 3*3 design. Study population: Adult patients with malignant mesothelioma who were treated with chemotherapy as standard treatment.
Intervention: After chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using specific cytokines. Pulsed autologous DCs (MesoCancerVac) are re-injected 3 times every two weeks. After the third injection with MesoCancerVac, revaccinations to boost the immune system are given after 3 and 6 months.
Main study parameters/endpoints: The aim of this phase I protocol is to study the toxicity and safety of MesoCancerVac (DC-based immunotherapy) in MM patients. Toxicities will be scored according to common toxicity criteria version 4.0. The following toxicities occurring during 8 weeks after the first vaccination, will be considered as dose-limiting toxicities (DLTs).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients have to undergo extra outdoor visits for this study (10-20) and extra invasive procedures especially for this trial, like a catheter in a blood vessel. These are invasive procedure but risks are limited. This iv entrance is necessary every time, for the leukopheresis, for blood samples and for the injection of the dendritic cells. A leucopheresis is a standard procedure and will be performed according to guidelines. There is a limited risk for transient thrombocytopenia and leukopenia.
The administration of autologous cells, that have been loaded with allogeneic human materials, is a potential risk and that is the subject of the study. Because not the lysate itself is administered to the patients but only when it is processed by the dendritic cells of the patient the investigators expect these risks to be limited.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MesoCancerVac | Experimental | Biological: MesoCancerVacAutologous dendritic cells loaded with a mixture of 5 allogenic mesothelioma tumor cell lysates 3 to 5 vaccinations with 10x10e6, 25x10e6 or 50x10e6 loaded dendritic cells i.d. and i.v. administration every two weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients with histological or cytological confirmed diagnosed ,malignant mesothelioma, who are non progressive after at least 4 cycles of cisplatin and pemetrexed containing chemotherapy (as determined by CT scanning).
- Measurable disease on CT scanning in two dimensions by a radiologic imaging study.
- Patients must be at least 18 years old and must be able to give written informed consent.
- Patients must be ambulatory (WHO performance status 0,1, or 2 [Appendix E\&F]) The expected survival must be at least 3 months.
Key exclusion criteria (13 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Medical or psychological impediment to probable compliance with the protocol.
- Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from that 6 weeks interval
- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for five years.
- Serious concomitant disease, or active infections.
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 |
|---|---|---|
| MesoCancerVacA leukapheresis is performed of which the monocytes are used for differentiation to DCs using specific cytokines. Pulsed autologous DCs (MesoCancerVac) are re-injected 3 times every two weeks. After the third injection with MesoCancerVac, revaccinations to boost the immune system are given after 3 and 6 months. | Biological | MesoCancerVac |
Primary outcome
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma
Time frame: 4 weeks after third administration
Tolerability of MesoCancerVac is monitored by performing clinical laboratory tests (autoimmune responses), assessments of vital signs, full clinical examination, occurrence of adverse events.
1 secondary outcome
The secondary objective is the evaluation of an immune response after MesoCancerVac
Time frame: 2 months after third administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2015.
- Background: PubMed 20167848Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90. doi: 10.1164/rccm.200909-1465OC. Epub 2010 Feb 18.
- Results publication: PubMed 22778767Cornelissen R, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. New roads open up for implementing immunotherapy in mesothelioma. Clin Dev Immunol. 2012;2012:927240. doi: 10.1155/2012/927240. Epub 2012 Jun 24.
- Results publication: PubMed 23148753Cornelissen R, Lievense LA, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Dendritic cell-based immunotherapy in mesothelioma. Immunotherapy. 2012 Oct;4(10):1011-22. doi: 10.2217/imt.12.108.
- Results publication: PubMed 15764728Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. doi: 10.1164/rccm.200501-057OC. Epub 2005 Mar 11.
- Derived from this study: PubMed 36104949van Gulijk M, Belderbos B, Dumoulin D, Cornelissen R, Bezemer K, Klaase L, Dammeijer F, Aerts J. Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma. Int J Cancer. 2023 Apr 1;152(7):1438-1443. doi: 10.1002/ijc.34293. Epub 2022 Oct 3.
- Derived from this study: PubMed 32234848Vroman H, Balzaretti G, Belderbos RA, Klarenbeek PL, van Nimwegen M, Bezemer K, Cornelissen R, Niewold ITG, van Schaik BD, van Kampen AH, Aerts JGJV, de Vries N, Hendriks RW. T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma. J Immunother Cancer. 2020 Mar;8(1):e000251. doi: 10.1136/jitc-2019-000251.
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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.
Henk C Hoogsteden, MD PhD study director
Erasmus Medical Center Cancer Institure
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 MesoCancerVac in people with Mesothelioma, run by Erasmus Medical Center at 1 site in Netherlands.
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 10 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: status not confirmed, as of the sponsor's last update on 23 Mar 2015. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joachim G. Aerts, MD PhD (+31 10 704 3697, j.aerts@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma (time frame: 4 weeks after third administration). 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 NCT02395679, which also lists 6 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 23 Mar 2015.