Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)
Brief 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.


Options:
A: Arm Label: Group 1; Type: EXPERIMENTAL; Interventions: Biological: Anti-GD2 antibody | Intervention Type: BIOLOGICAL; Name: Anti-GD2 antibody; Assigned to Arm(s): Group 1
B: Arm Label: R0: COJEC plus G-CSF; Type: EXPERIMENTAL; Interventions: Drug: Carboplatin, Drug: Etoposide, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: G-CSF | Arm Label: R0: COJEC; Type: ACTIVE_COMPARATOR; Interventions: Drug: Vincristine, Drug: Carboplatin, Drug: Etoposide, Drug: Cisplatin, Drug: Cyclophosphamide | Arm Label: R1: BuMel MAT; Type: ACTIVE_COMPARATOR; Interventions: Drug: Busulfan, Drug: Melphalan | Arm Label: R1: CEM MAT; Type: EXPERIMENTAL; Interventions: Drug: Carboplatin, Drug: Etoposide, Drug: Melphalan | Arm Label: R2: ch14.18/CHO; Type: ACTIVE_COMPARATOR; Interventions: Drug: ch14.18/CHO | Arm Label: R2: ch14.18/CHO plus Aldesleukin; Type: EXPERIMENTAL; Interventions: Drug: Aldesleukin, Drug: ch14.18/CHO | Arm Label: R3: COJEC Induction; Type: ACTIVE_COMPARATOR; Interventions: Drug: Vincristine, Drug: Carboplatin, Drug: Etoposide, Drug: Cisplatin, Drug: Cyclophosphamide | Arm Label: R3: Modified N7; Type: EXPERIMENTAL; Interventions: Drug: Vincristine, Drug: Etoposide, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Doxorubicin | Arm Label: R4: cnt inf ch14.18/CHO; Type: ACTIVE_COMPARATOR; Interventions: Drug: ch14.18/CHO | Arm Label: R4: cnt inf ch14.18/CHO plus Aldesleukin; Type: EXPERIMENTAL; Interventions: Drug: Aldesleukin, Drug: ch14.18/CHO | Intervention Type: DRUG; Name: Vincristine; Assigned to Arm(s): R0: COJEC, R3: COJEC Induction, R3: Modified N7 | Intervention Type: DRUG; Name: Aldesleukin; Assigned to Arm(s): R2: ch14.18/CHO plus Aldesleukin, R4: cnt inf ch14.18/CHO plus Aldesleukin | Intervention Type: DRUG; Name: ch14.18/CHO; Assigned to Arm(s): R2: ch14.18/CHO, R2: ch14.18/CHO plus Aldesleukin, R4: cnt inf ch14.18/CHO, R4: cnt inf ch14.18/CHO plus Aldesleukin | Intervention Type: DRUG; Name: Carboplatin; Assigned to Arm(s): R0: COJEC, R0: COJEC plus G-CSF, R1: CEM MAT, R3: COJEC Induction | Intervention Type: DRUG; Name: Etoposide; Assigned to Arm(s): R0: COJEC, R0: COJEC plus G-CSF, R1: CEM MAT, R3: COJEC Induction, R3: Modified N7 | Intervention Type: DRUG; Name: Cisplatin; Assigned to Arm(s): R0: COJEC, R0: COJEC plus G-CSF, R3: COJEC Induction, R3: Modified N7 | Intervention Type: DRUG; Name: Cyclophosphamide; Assigned to Arm(s): R0: COJEC, R0: COJEC plus G-CSF, R3: COJEC Induction, R3: Modified N7 | Intervention Type: DRUG; Name: Doxorubicin; Assigned to Arm(s): R3: Modified N7 | Intervention Type: DRUG; Name: G-CSF; Assigned to Arm(s): R0: COJEC plus G-CSF | Intervention Type: DRUG; Name: Busulfan; Assigned to Arm(s): R1: BuMel MAT | Intervention Type: DRUG; Name: Melphalan; Assigned to Arm(s): R1: BuMel MAT, R1: CEM MAT
C: Arm Label: Arm I (temozolomide, irinotecan hydrochloride, temsirolimus); Type: EXPERIMENTAL; Interventions: Drug: Irinotecan Hydrochloride, Other: Laboratory Biomarker Analysis, Drug: Temozolomide, Drug: Temsirolimus | Arm Label: Arm II (temozolomide, irinotecan hydrochloride, dinutuximab); Type: EXPERIMENTAL; Interventions: Biological: Dinutuximab, Drug: Irinotecan Hydrochloride, Other: Laboratory Biomarker Analysis, Biological: Sargramostim, Drug: Temozolomide | Intervention Type: BIOLOGICAL; Name: Dinutuximab; Assigned to Arm(s): Arm II (temozolomide, irinotecan hydrochloride, dinutuximab) | Intervention Type: DRUG; Name: Irinotecan Hydrochloride; Assigned to Arm(s): Arm I (temozolomide, irinotecan hydrochloride, temsirolimus), Arm II (temozolomide, irinotecan hydrochloride, dinutuximab) | Intervention Type: OTHER; Name: Laboratory Biomarker Analysis; Assigned to Arm(s): Arm I (temozolomide, irinotecan hydrochloride, temsirolimus), Arm II (temozolomide, irinotecan hydrochloride, dinutuximab) | Intervention Type: BIOLOGICAL; Name: Sargramostim; Assigned to Arm(s): Arm II (temozolomide, irinotecan hydrochloride, dinutuximab) | Intervention Type: DRUG; Name: Temozolomide; Assigned to Arm(s): Arm I (temozolomide, irinotecan hydrochloride, temsirolimus), Arm II (temozolomide, irinotecan hydrochloride, dinutuximab) | Intervention Type: DRUG; Name: Temsirolimus; Assigned to Arm(s): Arm I (temozolomide, irinotecan hydrochloride, temsirolimus)
D: Arm Label: Arm I (isotretinoin) (closed to accrual as of 4/16/2009); Type: ACTIVE_COMPARATOR; Interventions: Drug: Isotretinoin, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Other: Quality-of-Life Assessment | Arm Label: Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin); Type: EXPERIMENTAL; Interventions: Biological: Aldesleukin, Biological: Dinutuximab, Drug: Isotretinoin, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Other: Quality-of-Life Assessment, Biological: Sargramostim | Intervention Type: BIOLOGICAL; Name: Aldesleukin; Assigned to Arm(s): Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: BIOLOGICAL; Name: Dinutuximab; Assigned to Arm(s): Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: DRUG; Name: Isotretinoin; Assigned to Arm(s): Arm I (isotretinoin) (closed to accrual as of 4/16/2009), Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: OTHER; Name: Laboratory Biomarker Analysis; Assigned to Arm(s): Arm I (isotretinoin) (closed to accrual as of 4/16/2009), Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: OTHER; Name: Pharmacological Study; Assigned to Arm(s): Arm I (isotretinoin) (closed to accrual as of 4/16/2009), Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: OTHER; Name: Quality-of-Life Assessment; Assigned to Arm(s): Arm I (isotretinoin) (closed to accrual as of 4/16/2009), Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) | Intervention Type: BIOLOGICAL; Name: Sargramostim; Assigned to Arm(s): Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin)

Answer: B