Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients

NCT02395679 | Unknown Phase 1 DMC

• 1 other identifier: NL44330.000.14
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Mesothelioma

Keywords

Dendritic cell-based immunotherapy

Outcome Measures

Primary Outcomes (1)

• The primary objective is to establish a tolerable dose of MesoCancerVac in patients with malignant mesothelioma

  Tolerability of MesoCancerVac is monitored by performing clinical laboratory tests (autoimmune responses), assessments of vital signs, full clinical examination, occurrence of adverse events.

  4 weeks after third administration

Secondary Outcomes (1)

• The secondary objective is the evaluation of an immune response after MesoCancerVac

  2 months after third administration

Study Arms (1)

MesoCancerVac

EXPERIMENTAL

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

Biological: MesoCancerVac

Interventions

MesoCancerVac BIOLOGICAL

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.

MesoCancerVac

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Patients with histological or cytological confirmed diagnosed ,malignant mesothelioma, who are non progressive after at least 4 cycles of cisplatin and pemetrexed containing chemotherapy (as determined by CT scanning).
• Measurable disease on CT scanning 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 (WHO performance status 0,1, or 2 \[Appendix E\&F\]) The expected survival must be at least 3 months.
• Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count \> 1.0 x 10e9/l, platelet count \> 100 x 10e9/l, and Hb \> 6.0 mmol/l.(as determined during screening
• Positive delayed type hypersensitivity skin test (induration \> 2mm after 48 hrs) against at least one positive control antigen tetanus toxoid.
• Ability to return to the Erasmus Medical Center for adequate follow-up as required by this protocol.
• Written informed consent according to good clinical practice
• Planned start date of vaccination between 5 weeks after the last dosage of chemotherapy

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Medical or psychological impediment to probable compliance with the protocol.
• Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from that 6 weeks interval
• Prior malignancy except 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, or active infections.
• History of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV and viral hepatitis.
• 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.
• Known allergy to shell fish (may contain KLH).
• Pregnant or lactating women.
• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC, Dept. of Pulmonary Medicine

Rotterdam, South Holland, 3015GD, Netherlands

RECRUITING

Related Publications (6)

• Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90. doi: 10.1164/rccm.200909-1465OC. Epub 2010 Feb 18.

  PMID: 20167848 BACKGROUND

• Cornelissen R, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. New roads open up for implementing immunotherapy in mesothelioma. Clin Dev Immunol. 2012;2012:927240. doi: 10.1155/2012/927240. Epub 2012 Jun 24.

  PMID: 22778767 RESULT

• Cornelissen R, Lievense LA, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Dendritic cell-based immunotherapy in mesothelioma. Immunotherapy. 2012 Oct;4(10):1011-22. doi: 10.2217/imt.12.108.

  PMID: 23148753 RESULT

• Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. doi: 10.1164/rccm.200501-057OC. Epub 2005 Mar 11.

  PMID: 15764728 RESULT

• van Gulijk M, Belderbos B, Dumoulin D, Cornelissen R, Bezemer K, Klaase L, Dammeijer F, Aerts J. Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma. Int J Cancer. 2023 Apr 1;152(7):1438-1443. doi: 10.1002/ijc.34293. Epub 2022 Oct 3.

  PMID: 36104949 DERIVED

• Vroman H, Balzaretti G, Belderbos RA, Klarenbeek PL, van Nimwegen M, Bezemer K, Cornelissen R, Niewold ITG, van Schaik BD, van Kampen AH, Aerts JGJV, de Vries N, Hendriks RW. T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma. J Immunother Cancer. 2020 Mar;8(1):e000251. doi: 10.1136/jitc-2019-000251.

  PMID: 32234848 DERIVED

MeSH Terms

Conditions

Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Study Officials

• Henk C Hoogsteden, MD PhD

  Erasmus Medical Center Cancer Institure

  STUDY DIRECTOR

Central Study Contacts

Joachim G. Aerts, MD PhD

CONTACT

+31 10 704 3697; j.aerts@erasmusmc.nl

Cor H. van der Leest, MD PhD

CONTACT

+31 10 704 3697; k.vanderleest@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head production

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: March 23, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: March 23, 2015

Record last verified: 2015-03

Locations

NL (1)