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

Phase 1
Open (Enrolling)
Malignant (Pleural) Mesothelioma

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Trial Information

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

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

- 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)

Inclusion Criteria

Inclusion criteria:

- Patients with clinically and histological or cytological confirmed newly diagnosed
MM, that can be measured in two dimensions by a radiologic imaging study.

- Patients must be at least 18 years old and must be able to give written informed

- Patients must be ambulatory (Karnofsky scale > 70, or WHO-ECOG performance status
0,1, or 2) and in stable medical condition. The expected survival must be at least 4

- Patients must have normal organ function and adequate bone marrow reserve: absolute
neutrophil count > 1.5 x 109/l, platelet count > 100 x 109/l, and Hb > 6.0 mmol/l.

- Positive DTH skin test (induration > 2mm after 48 hrs) against at least one positive
control antigen tetanus toxoid.

- Stable disease or response after chemotherapy.

- Availability of sufficient tumor material of the patient.

- Ability to return to the Erasmus MC for adequate follow-up as required by this

- Able to tolerate oral therapy

- No impairment of gastrointestinal (GI) function or GI disease that may affect or
alter absorption of CTX (e.g., mal-absorption syndrome, history of total
gastrectomy/significant small bowel resection)

- No history of allergic reactions (≥ grade 3 or 4) to compounds of similar chemical or
biologic composition to CTX (i.e., alkylating agents)

- No known intolerance or hypersensitivity reaction to CTX

Exclusion criteria:

- Conditions that make the patient unfit for chemotherapy or progressive disease after
4 cycles of chemotherapy.

- Pleurodesis at the affected side before the pleural fluid is obtained.

- Medical or psychological impediment to probable compliance with the protocol.

- Patients on steroid (or other immunosuppressive agents) are excluded on the basis of
potential immune suppression. Patients must have had 6 weeks of discontinuation and
must stop of any such treatment during the time of the study.

- No prior malignancy is allowed except for 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, no active infections. Patients with a history of
autoimmune disease or organ allografts, or with active acute or chronic infection,
including HIV (as determined by ELISA and confirmed by Western Blot) and viral
hepatitis (as determined by HBsAg and Hepatitis C serology).

- Patients with 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.

- Patients with a known allergy to shell fish (may contain KLH).

- Pregnant or lactating women.

- Patients with 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

number of cytotoxic T cells and regulatory T cells in the blood of patients

Outcome Description:

2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.

Outcome Time Frame:

up to 1 year

Safety Issue:


Principal Investigator

Joachim Aerts, PhD MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Erasmus Medical Center


Netherlands: Centrale Commissie Mensgebonden Onderzoek

Study ID:




Start Date:

October 2009

Completion Date:

October 2012

Related Keywords:

  • Malignant (Pleural) Mesothelioma
  • Mesothelioma
  • Dendritic cells
  • Cyclophosphamide
  • Tumor lysate-loaded
  • Immunotherapy
  • Mesothelioma