High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)

Summary

This is a randomized study of the European SIOP Neuroblastoma Group (SIOPEN) in high-risk neuroblastoma (stages 2, 3, 4 and 4s MYCN-amplified neuroblastoma, stage 4 MYCN non amplified \> 12 months at diagnosis).

The protocol consists of a rapid, dose intensive induction chemotherapy, peripheral blood stem cell harvest, attempted complete excision of the primary tumour, myeloablative therapy followed by peripheral blood stem cell rescue, radiotherapy to the site of the primary tumour and immunotherapy (R4 randomization - isotretinoin and ch14.18/CHO (Dinutuximab beta, Qarziba ®).), with or without s.c. aldesleukin (IL-2)). Patients diagnosed after the closure of R3 randomization will not be R4 randomized. For these patients the use of ch14.18/CHO antibody is recommended without scIL-2 as continuous infusion as standard of care outside of controlled trials. ch14.18/CHO received marketing authorization by EMA in May 2017 (Qarziba ®).

In the induction phase, all patients receive Rapid COJEC following the result of the R3 randomization which was closed on June 8th, 2017 after inclusion of 630 patients as planned.

Following induction treatment peripheral blood stem cell harvest (PBSCH) is performed and complete excision of the primary tumour will be attempted.

Patients with an inadequate metastatic response to allow BuMel MAT followed by PBSCR at the end of induction should receive 2 TVD (Topotecan, Vincristine, Doxorubicin) cycles.

After Rapid COJEC induction, localized patients will proceed to consolidation. Patients aged 12-18 months at diagnosis, with stage 4 neuroblastoma, no MYCN amplification and without segmental chromosomal alterations (SCAs) are thought to have a good prognosis and will stop treatment after induction therapy and surgery to the primary tumour.

Consolidation consists of BuMel MAT based on the results of the R1 randomization followed by peripheral blood stem cell rescue (PBSCR) and radiotherapy to the site of the primary tumour.

The R2 immunotherapy randomization using ch14.18/CHO as 8 hour infusion on 5 consecutive days ( total dose (100mg/m²) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) is closed.

The amended R4 immunotherapy randomization using ch14.18/CHO as continuous infusion (total dose 100mg/m² over 10 days) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) has accrued according to plan with results pending awaiting data maturity and DMC approval.

Conditions

• Neuroblastoma

Interventions

DRUG

Vincristine

given during Rapid COJEC and modified N7 therapy

DRUG

Aldesleukin

Aldesleukin is given during MRD Treatment for patients randomised to the arm with IL-2

DRUG

ch14.18/CHO

ch14.18/CHO antibody is given during MRD treatment

DRUG

Carboplatin

Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)

DRUG

Etoposide

Etoposide is given during Induction Treatment (both R3 randomisation arms)

DRUG

Cisplatin

Cisplatin is given during Induction Treatment (both R3 randomisation arms)

DRUG

Cyclophosphamide

Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)

DRUG

Doxorubicin

Doxorubicin is given during Induction Treatment (R3 arm modified N7)

DRUG

G-CSF

G-CSF is given during Induction Treatment

DRUG

Busulfan

In case i.v. busulfan is not available, the use of oral busulfan is permitted, although not recommended.

DRUG

Melphalan

Melphalan is given during MAT treatment

Sponsors & Collaborators

• St. Anna Kinderkrebsforschung

  lead OTHER

Principal Investigators

• Ruth L Ladenstein, MD, MBA, cPM · St. Anna Kinderkrebsforschung

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Month

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-02-28

Primary Completion

2021-09-30

Completion

2026-09-30

Countries

• Australia
• Austria
• Belgium
• Czechia
• Denmark
• France
• Greece
• Hungary
• Ireland
• Israel
• Italy
• Norway
• Poland
• Portugal
• Slovakia
• Slovenia
• Spain
• Sweden
• Switzerland
• United Kingdom

Study Locations