Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma

Phase 1

Completed

• Conditions: Malignant (Pleural) Mesothelioma
• Interventions: Biological: DC + CTX

• Registration Number: NCT01241682
• Lead Sponsor: Erasmus Medical Center

Brief Summary

Earlier the investigators determined the safety and feasibility of tumor lysate-pulsed dendritic cells as therapeutic adjuvants in mesothelioma patients. Because pre-clinical data in mice had shown that better results were obtained when regulatory T cells were depleted using low-dosis of cyclophosphamide, ten patients who responded on chemotherapy are selected for DC-treatment in combination with Endoxan.

Detailed Description

Currently there is no satisfactory low-toxicity treatment for patients with mesothelioma (MM). Based on studies in other types of cancer in humans where beneficial effects were obtained, and based on our pre-clinical data in a mouse model for MM, led to the introduction of DC-immunotherapy for human MM in 2005. A beneficial effect of immunotherapy in MM patients without major side effects was found, however, research has shown that DC immunotherapy might be further improved. The objectives of the here proposed phase study are:

* To define the safety and toxicity of low dose CTX in combination with MesoCancerVac in patients with MM.

* To determine if vaccination with low dose CTX in combination with MesoCancerVac results in a detectable immune response by skin DTH reactions on MM crude antigen and KLH and by in vitro laboratory analysis.

* To observe and document anti-cancer activity by laboratory evaluation (e.g. decrease in Tregs, increase in CTLs using 51Cr release and IFN-gamma ELISPOT)

* To observe and document anti-cancer activity by clinical evaluation (e.g. CT scan)

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2010-06-01
• Study First Submitted QC: 2010-11-15
• Study First Posted: 2010-11-16
• Primary Completion: 2011-10
• Study Completion: 2012-10
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-26
• Last Update Posted: 2014-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DC immunotherapy + CTX	DC + CTX	Patients with mesothelioma who are fit enough to be treated with chemotherapy and enough tumor material was available are asked for participation in this study. After 4 cycles of Alimta chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using different cytokines. The procedure to grow DCs in vitro and pulse them with tumor lysate is performed according to our earlier performed phase I study that was approved by our local ethics committee. Three doses of properly pulsed autologous DCs (MesoCancerVac) are then re-injected every two weeks. Patients will be treated with a low dose of CTX for seven day in a row the week before the 1st vaccination, the weeks in between the 2nd, and for one week after the 3rd vaccination.

Primary Outcome Measures

Name	Time	Method
number of cytotoxic T cells and regulatory T cells in the blood of patients	up to 1 year	2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.

Secondary Outcome Measures

Name	Time	Method
safety and toxicity	up to 2 years

Trial Locations

Locations (1)

Erasmus Medical Center; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands