Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients (MesoCancerVa)

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 ] [ Designated as safety issue: Yes ]
• 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 Measure

  • The secondary objective is the evaluation of an immune response after MesoCancerVac [ Time Frame: 2 months after third administration ] [ Designated as safety issue: No ]
    Immune response is evaluated by measuring : The functionality of T-cells by laboratory testing (cytotoxicity and interferon-gamma secretion)

  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.

  Eligibility

  Criteria

  Inclusion 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 >l; 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

  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.