High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)
Status:
Recruiting
Trial end date:
2026-09-01
Target enrollment:
Participant gender:
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.