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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
joost hegmans, Erasmus Medical Center
ClinicalTrials.gov Identifier:
NCT01241682
First received: June 1, 2010
Last updated: February 26, 2014
Last verified: February 2014

June 1, 2010
February 26, 2014
October 2009
October 2011   (final data collection date for primary outcome measure)
number of cytotoxic T cells and regulatory T cells in the blood of patients [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.
Same as current
Complete list of historical versions of study NCT01241682 on ClinicalTrials.gov Archive Site
safety and toxicity [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma
Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma

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.

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)
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant (Pleural) Mesothelioma
Biological: DC + CTX
3x 50x10e6 DC + cyclophosphamide
Other Name: Endoxan
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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
October 2012
October 2011   (final data collection date for primary outcome measure)

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.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01241682
NL24050.000.08
Yes
joost hegmans, Erasmus Medical Center
Erasmus Medical Center
Not Provided
Principal Investigator: Joachim Aerts, PhD MD Erasmus Medical Center
Erasmus Medical Center
February 2014

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