Brief Title
Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients
Official Title
A Phase I Study on Dendritic Cells Loaded With Allogeneous Cell Lysate in Patients With Mesothelioma as Maintenance Treatment After Chemotherapy
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma
Secondary Outcome
The secondary objective is the evaluation of an immune response after MesoCancerVac
Condition
Mesothelioma
Intervention
MesoCancerVac
Study Arms / Comparison Groups
MesoCancerVac
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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
9
Start Date
January 2015
Completion Date
December 2016
Primary Completion Date
December 2015
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Henk C Hoogsteden, MD PhD, +31 10 704 3697, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT02395679
Organization ID
NL44330.000.14
Responsible Party
Principal Investigator
Study Sponsor
Erasmus Medical Center
Study Sponsor
Henk C Hoogsteden, MD PhD, Study Director, Erasmus Medical Center Cancer Institure
Verification Date
March 2015