HIT - HGG Rez Immunovac

Autor: Julia Dobke, erstellt am: 10.10.2018, Zuletzt geändert: 15.10.2018

Titel Autologous Dendritic Cells and Metronomic Cyclophosphamide for Relapsed High Grade Gliomas in Children and Adolescents HIT - HGG Rez Immunovac
Erkrankung Rezidiv eines hochgradig malignen Glioms
Art Prospektive, nicht randomisierte, einarmige, multizentrische Phase I/II Studie.
Fragestellung / Ziel

Rezidivierte hochgradig maligne Gliome (HGG) bei Kindern und Jugendlichen representieren eine Erkrankungsgruppe mit einer sehr schlechten Prognose, für die es keine aktuell empfohlene Standardtherapie gibt.
Die Studie evaluiert die Effektivität einer Kombinationstherapie von metronomisch verabreichtem oralem Cyclophosphamid und autologen tumor-lysate Dendritischen Zellen (DCs) gemessen am 6-Monatsüberleben nach Tumorresektion.

Therapie / Studienarme

Studienpatienten erhalten täglich ab Rezidivdiagnose und Einschluss in die Studie 100 mg Cyclophospamid (1,5 mg/kg/d, max. 100 mg) aufgeteilt in 2 Dosen bis zum Tag vor der 1. DC-Impfung.
Sieben bis zehn Tage nach Ende der periioperativen Steroidtherapie erfolgt eine unstimulierte Leukapharese. Neun Tage nach der Leukapherese erfolgen mit wöchentlichem Abstand vier Impfungen mit DCs, danach drei Impfungen alle vier Wochen und dann solange 3-monatlich, bis der Impfstoff verbraucht ist.

Einschluss-Kriterien
  • Diagnosis of high-grade malignant glioma confirmed by central neuropathological review (last MRI diagnosis not older than 4 weeks) - including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (analogous to WHO
  • III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) - relapsed after first-line therapy.
  • Male and female patients aged 3 years and older but under 21 years at time of relapse diagnosis
  • Written informed consent of patients (18-21 years) or the parents (mandatory till 18 years of age). A patient information will be provided for children aged 7-11 years, and adolescents aged 12-18 years. A signed informed consent should be obtained from young adults from the age of 14 years onward.
  • High probability to get at least 300 mg resected tumour tissue (corresponding to 1.44 mg tumour protein) and to undergo an unstimulated leukapheresis.
  • High probability to totally or subtotally resect the relapsed tumour.
  • High probability to wean postoperative steroids within 14 days after neurosurgery.
Ausschluss-Kriterien
  • Known hypersensitivity or contraindication to investigational medicinal study product (IMP) or to cyclophosphamide or imiquimod
  • 2Other malignancies, either simultaneous or within the last 2 years
  • Pregnancy and / or lactation
  • Patients who are sexually active refusing to undergo regular pregnancy tests and use of a highly effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile)
  • Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
  • Severe concomitant diseases (e.g. immune deficiency syndrome)
  • Severe psychological disease or neurological damage without possibility to communicate
  • Clinical signs of intracranial pressure
  • Intracerebral hemorrhage or gliomatosis
  • No severe blood count abnormalities: leukocytes < 2.000/μl, Hb <10 g/dl, thrombocytes <100.000/μl
  • No severe liver enzyme elevation (> 2-3x fold of normal)
  • Ongoing reirradiation or chemotherapy within the last 4 weeks (irradiation of formerly noninvolved fields is allowed, but not part of this study)
  • Estimated life expectancy of less than 2 months
  • Preexisting severe cardiac disease
  • Presence of unresectable spinal metastases
  • Karnofsky/Lansky index < 50%
  • Active infection within the last 2 weeks
  • Previous infection with HIV, HCV, HTLV1/2, HBV (unless > 5 year ago and αHBs >100 U/ml), Lues, protozoan parasites, or other chronic bacterial infections.
  • With regard to prevention of variant Creutzfeldt-Jakob disease (vCJD) the following patients have to be excluded: patients living in the UK between 1980 and 1996 for more than 6 months, patients with a personal or family history of vCJD, recipients of GH or TSH of human origin,recipients of dura mater or cornea transplants.
  • Patients receiving systemic immunosuppressant or immunoactivating substances
Patientenanzahl 25
Status Start: 01.02.2018 Ende: 31.01.2021
EudraCT 2013 - 000419 - 26
Eintrag Studien- Register
Leiter Prof. Dr. Matthias Eyrich
E-Mail mailto:eyrich _m@ukw.de
Kontakt

Leitung
Prof. Dr. Matthias Eyrich
Universitaets-Kinderklinik Wuerzburg
Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany
phone: +49 (931) 201-27728
fax: +49 (931) 201-27887
email: eyrich_m@ukw.de

Vertreter
Prof. Dr. Paul G. Schlegel
phone: +49 (931) – 201 - 27728
fax: +49 (931) – 201 - 27887
email: schlegel@mail.uni-wuerzburg.de

Weitere Informationen Sponsor: Universitaetsklinikum Wuerzburg
Förderung Deutsche Kinderkrebsstiftung.