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Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma (PMR-MM-002)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01241682
Recruitment Status : Completed
First Posted : November 16, 2010
Last Update Posted : February 27, 2014
Information provided by (Responsible Party):
joost hegmans, Erasmus Medical Center

Tracking Information
First Submitted Date  ICMJE June 1, 2010
First Posted Date  ICMJE November 16, 2010
Last Update Posted Date February 27, 2014
Study Start Date  ICMJE October 2009
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2010)
number of cytotoxic T cells and regulatory T cells in the blood of patients [ Time Frame: up to 1 year ]
2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2010)
safety and toxicity [ Time Frame: up to 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma
Official Title  ICMJE Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant (Pleural) Mesothelioma
Intervention  ICMJE Biological: DC + CTX
3x 50x10e6 DC + cyclophosphamide
Other Name: Endoxan
Study Arms  ICMJE Experimental: DC immunotherapy + 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.
Intervention: Biological: DC + CTX
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 15, 2010)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 consent.
  • 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 months.
  • 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 protocol.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01241682
Other Study ID Numbers  ICMJE NL24050.000.08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party joost hegmans, Erasmus Medical Center
Study Sponsor  ICMJE Erasmus Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joachim Aerts, PhD MD Erasmus Medical Center
PRS Account Erasmus Medical Center
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP