Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients

Phase 1

• Conditions: Mesothelioma
• Interventions: Biological: MesoCancerVac

• Registration Number: NCT02395679
• Lead Sponsor: Erasmus Medical Center

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 Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-30
• Status Verified: 2015-03
• Study First Submitted QC: 2015-03-17
• Last Update Submitted: 2015-03-17
• Study First Posted: 2015-03-23
• Last Update Posted: 2015-03-23
• Primary Completion: 2015-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MesoCancerVac	MesoCancerVac	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

Primary Outcome Measures

Name	Time	Method
The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma	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.

Secondary Outcome Measures

Name	Time	Method
The secondary objective is the evaluation of an immune response after MesoCancerVac	2 months after third administration	Immune response is evaluated by measuring : The functionality of T-cells by laboratory testing (cytotoxicity and interferon-gamma secretion)

Trial Locations

Locations (1)

Erasmus MC, Dept. of Pulmonary Medicine; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands