Download PDF

Clinical Trial Results:
A PHASE I/II DOSE SCHEDULE FINDING STUDY OF CH14.18/CHO CONTINUOUS INFUSION COMBINED WITH SUBCUTANEOUS ALDESLEUKIN (IL-2) IN PATIENTS WITH PRIMARY REFRACTORY OR RELAPSED NEUROBLASTOMA. A SIOPEN STUDY.

Summary
EudraCT number	2009-018077-31
Trial protocol	AT ES DE IT GB IE PL BE
Global end of trial date	30 Jan 2025

Results information
Results version number	v1(current)
This version publication date	04 Mar 2026
First version publication date	04 Mar 2026
Other versions
Summary report(s)	LTI_EoT Final Report Summary_Layperson Version_09-02-2026

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

012010

ISRCTN number

US NCT number

NCT01701479

WHO universal trial number (UTN)

Other trial identifiers

LTI - Long Term continuous Infusion: LTI

Sponsor organisation name

St. Anna Kinderkrebsforschung

Sponsor organisation address

Zimmermannplatz 10, Wien, Austria, 1090

Public contact

Ruth Ladenstein, St. Anna Children's Cancer Research Institute, +43 1404704775, ruth.ladenstein@stanna.at

Scientific contact

Ruth Ladenstein, St. Anna Children's Cancer Research Institute, +43 1404704775, ruth.ladenstein@stanna.at

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

31 Jan 2025

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Jan 2025

Was the trial ended prematurely?

Main objective of the trial

In the V1+V2 population the main objective was to to find an improved treatment schedule which reduces the pain-toxicity profile of ch14.18/CHO whilst maintaining immunomodulatory efficacy in patients (1-21 years old) with primary refractory (≥ 2 lines of conventional treatment) or relapsed neuroblastoma through prolonged continuous infusion in combination with s.c. aldesleukin (IL-2). In the V3 population the main objective was the clarification of the role of sc IL-2 on event free survival by randomising the standard arm against the ch14.18/CHO only treatment arm. This decision was based on the V1+V2 population toxicity profiles and sc IL-2 toxicity data from the HR-NBL1 SIOPEN trial. The use of isotretinoin remained unchanged in both treatment arms.

Protection of trial subjects

Detailed supportive care measures have been specified in the trial Protocol, section 8.6. One aim of this study was to reduce the extent of neuropathic pain by administering the antibody as a prolonged continuous infusion to develop a schedule ultimately allowing for outpatient management of patients on trial. Therefore, this study aimed to establish a standard pain prophylaxis without the use of high doses of intravenous morphine. However, since neuropathic pain is an anticipated side effect even in a prolonged continuous infusion setting, children were to receive premedication with gabapentin (Neurontin®) from at least 3 days prior to the start of the ch14.18/CHO, as well as intravenous morphine prior to and during antibody infusion as required. Concomitant standard pain management was to be established with or without i.v. morphine and followed standard WHO guidelines including medications as follows: Pain management/premedication: - Prior to receiving ch14.18/CHO the patient should be primed with oral gabapentin, starting 3 days prior to the start of the ch14.18/CHO infusion. The recommended oral dose of gabapentin is 10 mg/kg/dose once daily on day 1, increasing to 10 mg/kg/dose twice daily on day 2 and 10 mg/kg three times a day thereafter. Gabapentin could either be stopped at the end of each continuous antibody infusion (and restarted 3 days prior to subsequent cycle) or continued throughout cycles and stopped after the end of the last infusion, according to local guidelines. Gabapentin was available as oral solution containing 250 mg/5 mL of gabapentin or in capsules (100 mg, 300 mg, and 400 mg). The maximum single dose for Gabapentin is 300 mg. - Premedication with anti-inflammatory drugs (e.g. paracetamol, metamizol according to local guidelines) was recommended prior to each dose of recombinant human Interleukin-2 (rhIL-2; Proleukin) to reduce anticipated toxicities.

Background therapy

V1 and V2 (section 4 Trial Design) explored a feasible schedule for the LTI ch14.187CGO setting in patients with primary refractory or relapsed neuroblastoma. The dose and schedule of scIL-2 and isotretinoin (13-cis-RA) were constant. 20-40 patients were enrolled within the dose schedule finding part of the study with additional 20 patients enrolled during the confirmatory phase. International Amendment 1 extended the confirmatory cohort to an expansion cohort of a total of 100 patients. Three dose levels of ch14.18/CHO dose levels were considered in V1 with respect to daily dose: 7 mg/m², 10 mg/m² and 15 mg/m² whilst the infusion durations in this design had a range from 10 to 21 days. In V2 the ch14.18/CHO was administered as a diluted solution for infusion over a period of 10 days at a dose of 10 mg/m²/day within each treatment cycle by continuous infusion.

Evidence for comparator

In V3 the LTI ch14.18/CHO only treatment arm was compared with the standard arm as established in V2. The use of retinoid remained unchanged in both treatment arms.

Actual start date of recruitment

25 Jan 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Scientific research, Efficacy

Long term follow-up duration

3 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country