Longterminfusion Study (LTI)

Author: Prof. Dr. med. Holger Lode, Julia Dobke, erstellt am: 2012/04/11, Last modification: 2012/06/13

Title A Phase I/II Dose Schedule Finding Study of ch14.18/CHO Continuous Infusion Combined with Subcutaneous Aldesleukin (=Proleukin) (IL-2) in Patients with Primary Refractory or Relapsed Neuroblastoma. A SIOPEN Study.
Disease Primary refractory or relapsed Neuroblastoma
Type Prospective, non-blinded, open-label, dose schedule finding, multi-centre phase I/II study
Problem / Objectives

The immunotherapy of neuroblastoma with ch14.18 antibody is an effective therapeutical option, with severe pain from neuropathia as an main side effect.
This trial examines, if the prolongation of the ch14.18/CHO infusion (24 hrs longterminfusion for at least 10 days; dayly dose 10mg/m²) can establish an applicationform of the antibody, that is feasible without the support of i.v. morphine and which makes an ambulant therapy possible.
Until now it was necessary to treat patients with i.v. morphine during therapy with ch 14.18/CHO to controll the pain.

Important endpoints of this trial are the immune modulation effects of the therapy (ADCC, CDC, NK-cell activation), and to determine the pharmacokinetics of ch14.18/CHO.

Primary endpoint:
To find a tolerable treatment schedule which reduces the pain-toxicity profile of ch14.18/CHO whilst maintaining immunomodulatory efficacy in patients (1-21 years old) with either primary refractory (≥ 2 lines of conventional treatment) or relapsed neuroblastoma by using a prolonged continuous infusion in combination with s.c proleukin (IL-2).

Secondary endpoints:
• To assess pain intensity and relief by appropriate medication with a validated self- report tool. .
• To validate, during the first course, the correlation between activated NK cells and ch14.18/CHO level with ADCC by using MNC and serum from patients on day 15.
• To determine systemic immune modulation/response resulting from the combined treatment of ch14.18/CHO and s.c. proleukin (IL-2) by repeated analysis of NK-cell activation, soluble IL-2 receptor, ADCC, CDC and anti-idiotype response (HAMA and HACA).
• To achieve an increase in absolute lymphocyte counts and absolute NK cell numbers after the respective cycles as a measurement of response to s.c. proleukin (IL-2).
• To determine the pharmacokinetics of ch14.18/CHO.
• To evaluate anti-tumour responses resulting from this treatment regimen through clinical assessments in patients with measurable disease.
• To confirm the results of the chosen ch14.18/CHO infusion schedule in an expansion cohort of 20 patients

Therapy / Study arms

Immunotherapy with ch14.18 antibody as an 24 hrs longterminfusion over at leat 10 days; dayly dose 10 mg/m².

Inclusion Criteria
  • Histological confirmed neuroblatoma
  • At least one high dose treatment followed by stem cell rescue after conventional therapy
  • Treated and responding local relapse without progress of desease at timepoint of inclusion
  • Treated an responding disseminated relapse after primary localized neuroblastoma witout progression of dedease at timepoint of inclusion
Recruitment Minimum N = 20 patients, Maximum N = 60 patients
Status Recruitment: 01.04.2012-31.03.2014
EudraCT 2009-018077-31
Entry Study Register
Principal Investigator Prof. Dr. med. H. Lode, Prof. Dr. med. R. Ladenstein
Contact

Principal investigators

Prof. Dr. Holger Lode
Universitätsklinikum Greifswald
Allg. Pädiatrie mit Poliklinik/Päd. Onkologie
Ferdinand-Sauerbruch-Str.
17475 Greifswald
Telefon +49 (3834) 86 6301
Fax +49 (3834) 86 6410
holger.lode@uni-greifswald.de

Prof. Dr. med. Ruth Ladenstein
St. Anna-Kinderspital
Children´s Cancer Research Institute (CCRI)
Kinderspitalgasse 6
1090 Wien
Telefon +43 (1) 40470 4750
Fax +43 (1) 40470 7430
ruth.ladenstein@ccri.at

Participants University Children's Hospital, Greifswald, Germany St. Anna Children’s Hospital, Vienna, Austria Great Ormond Street, London, UK Gaslini Children’s Hospital, Genova, Italy Hospital Universitario La Fe, Valencia, Spain Institut Curie, Paris, France Institut Gustave Roussy, Villejuif, France Schneider Children’s Medical Centre of Israel, Petach Tikvah, Israel Sydney Children’s Hospital, Sydney, Australia
Weitere Informationen Funds:
The antibody production was based on a national SIOPEN fundraising. The database and trial is supported by the SIOPEN association. Further financial support: Hector-Stiftung (Prof. Lode).
Sponsoring Sponsor:
St. Anna Kinderkrebsforschung (international)
Children’s Cancer Research Institute (CCRI)
Zimmermannplatz 10, A-1090 Vienna, Austria

Universitätsmedizin Greifswald (national)
Fleischmannstrasse 8, 17475 Greifswald