Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients (MesoCancerVa)
Primary Purpose
Mesothelioma
Status
Unknown status
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
MesoCancerVac
Sponsored by
About this trial
This is an interventional treatment trial for Mesothelioma focused on measuring Dendritic cell-based immunotherapy
Eligibility Criteria
Inclusion criteria
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
- 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
Exclusion criteria
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.
- 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.
Sites / Locations
- Erasmus MC, Dept. of Pulmonary MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MesoCancerVac
Arm Description
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
Full Information
NCT ID
NCT02395679
First Posted
January 30, 2015
Last Updated
March 17, 2015
Sponsor
Erasmus Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02395679
Brief Title
Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients
Acronym
MesoCancerVa
Official Title
A Phase I Study on Dendritic Cells Loaded With Allogeneous Cell Lysate in Patients With Mesothelioma as Maintenance Treatment After Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Unknown status
Study Start Date
January 2015 (undefined)
Primary Completion Date
December 2015 (Anticipated)
Study Completion Date
December 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma
Keywords
Dendritic cell-based immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MesoCancerVac
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
MesoCancerVac
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma
Description
Tolerability of MesoCancerVac is monitored by performing clinical laboratory tests (autoimmune responses), assessments of vital signs, full clinical examination, occurrence of adverse events.
Time Frame
4 weeks after third administration
Secondary Outcome Measure Information:
Title
The secondary objective is the evaluation of an immune response after MesoCancerVac
Description
Immune response is evaluated by measuring :
The functionality of T-cells by laboratory testing (cytotoxicity and interferon-gamma secretion)
Time Frame
2 months after third administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
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
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
Exclusion criteria
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joachim G. Aerts, MD PhD
Phone
+31 10 704 3697
Email
j.aerts@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Cor H. van der Leest, MD PhD
Phone
+31 10 704 3697
Email
k.vanderleest@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henk C Hoogsteden, MD PhD
Organizational Affiliation
Erasmus Medical Center Cancer Institure
Official's Role
Study Director
Facility Information:
Facility Name
Erasmus MC, Dept. of Pulmonary Medicine
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cor P. van der Leest, PhD
Phone
+31 10 703 4862
Email
k.vanderleest@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Robin Cornelissen, PhD
Phone
+31 10 703 4862
Email
r.cornelissen@erasmusmc.nl
12. IPD Sharing Statement
Citations:
PubMed Identifier
20167848
Citation
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.
Results Reference
background
PubMed Identifier
22778767
Citation
Cornelissen 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 Reference
result
PubMed Identifier
23148753
Citation
Cornelissen 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 Reference
result
PubMed Identifier
15764728
Citation
Hegmans 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.
Results Reference
result
PubMed Identifier
32234848
Citation
Vroman 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. Erratum In: J Immunother Cancer. 2020 Jun;8(1):
Results Reference
derived
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Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients
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