- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01241682
Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma (PMR-MM-002)
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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)
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Zuid-Holland
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Rotterdam, Zuid-Holland, Pays-Bas, 3000 CA
- Erasmus Medical Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Enfant
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
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3x 50x10e6 DC + cyclophosphamide
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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number of cytotoxic T cells and regulatory T cells in the blood of patients
Délai: up to 1 year
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2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.
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up to 1 year
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
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safety and toxicity
Délai: up to 2 years
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up to 2 years
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Joachim Aerts, PhD MD, Erasmus Medical Center
Publications et liens utiles
Publications générales
- 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.
- 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.
- Veltman JD, Lambers ME, van Nimwegen M, de Jong S, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity. J Biomed Biotechnol. 2010;2010:798467. doi: 10.1155/2010/798467. Epub 2010 May 23.
- Cornelissen R, Hegmans JP, Maat AP, Kaijen-Lambers ME, Bezemer K, Hendriks RW, Hoogsteden HC, Aerts JG. Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma. Am J Respir Crit Care Med. 2016 May 1;193(9):1023-31. doi: 10.1164/rccm.201508-1573OC.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Tumeurs par type histologique
- Tumeurs
- Maladies pulmonaires
- Tumeurs par site
- Tumeurs, glandulaires et épithéliales
- Tumeurs des voies respiratoires
- Tumeurs thoraciques
- Tumeurs pulmonaires
- Adénome
- Tumeurs mésothéliales
- Tumeurs pleurales
- Mésothéliome
- Mésothéliome malin
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antirhumatismaux
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Cyclophosphamide
Autres numéros d'identification d'étude
- NL24050.000.08
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Malignant (Pleural) Mesothelioma
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Oregon Health and Science UniversityThe Gerber FoundationComplétéÉpanchement pleural chyleux après chirurgie cardiothoraciqueÉtats-Unis
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NRG OncologyNational Cancer Institute (NCI)RésiliéMésothéliome biphasique pleural | Mésothéliome épithélioïde pleural | Mésothéliome malin pleural de stade I AJCC v8 | Mésothéliome malin pleural de stade IA AJCC v8 | Mésothéliome malin pleural de stade IB AJCC v8 | Mésothéliome malin pleural de stade II AJCC v8 | Mésothéliome malin pleural...États-Unis, Canada
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Recrutement
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Samsung Medical CenterComplétéÉpanchement pleural unilatéralCorée, République de
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Naestved HospitalRésiliéÉpanchement pleural malin | Épanchement pleural exsudatifDanemark
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Aly Sherif HassaballaComplété
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Guy's and St Thomas' NHS Foundation TrustComplétéÉpanchement pleural malin | Cathéter pleural à demeureRoyaume-Uni
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Beijing Chao Yang HospitalInconnueÉpanchement pleural bilatéralChine
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RS Oncology LLCRecrutementMésothéliome | Mésothéliome pleural malin | Épanchement pleural malin | Mésothéliomes Pleural | Épanchement pleural malin | Mésothéliome ; PoumonRoyaume-Uni
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Scarlata, Simone, M.D.InconnueÉchographie thoracique | Trouble d'épanchement pleuralItalie
Essais cliniques sur DC + CTX
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DICE Therapeutics, Inc.ComplétéVolontaires en bonne santéPays-Bas
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Institut National de la Santé Et de la Recherche...ComplétéAccident vasculaire cérébral | AphasieFrance
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Pusan National UniversityInconnueAccident vasculaire cérébralCorée, République de
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Freie Universität BerlinComplétéTrouble de la personnalité limite
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Beijing Doing Biomedical Co., Ltd.Inconnue
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Iris SommerInconnueTroubles de la personnalité | Troubles psychotiques | Troubles de l'humeur | Troubles de stress, post-traumatique | Troubles auditifsPays-Bas
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Qingdao UniversityInconnue
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Universitätsklinikum Hamburg-EppendorfActif, ne recrute pasAccident vasculaire cérébralAllemagne, L'Autriche, Italie
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The University of New South WalesComplétéDépression majeureAustralie
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The University of New South WalesComplétéDépression majeureAustralie