ANBL0032
Phase III Randomized Study of Chimeric Antibody 14.18 (Ch14.18) in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue
Phase 3N = 226NCT00026312
- Population
- Patients with high-risk neuroblastoma who had responded to induction therapy and stem-cell transplantation; 226 eligible patients were randomised (patients with biopsy-proven residual disease after transplantation were assigned to immunotherapy non-randomly and excluded from the primary analysis).
- Design
- Randomised 1:1 (Children's Oncology Group): six cycles of isotretinoin with or without five cycles of ch14.18 (dinutuximab) with alternating GM-CSF and interleukin-2, after response to induction therapy and stem-cell transplantation. Randomisation stopped early for efficacy; intention-to-treat comparison of event-free survival.
- Primary endpoint
- EFS
- Arms
- Isotretinoin alone (control, n = 113): Six cycles of isotretinoin (13-cis-retinoic acid)
- Isotretinoin plus ch14.18, GM-CSF and IL-2 (experimental, n = 113): Six cycles of isotretinoin plus five concomitant cycles of ch14.18 (dinutuximab) with alternating GM-CSF and interleukin-2
- People
- Yu AL, senior author Sondel PM, Children's Oncology Group
Δ 24-month EFS+20 pointsΔ 24-month OS+11 pointsΔ 60-month EFS+10.5 pointsΔ 60-month OS+16.6 points
Show the numbers
| Endpoint | Analysis | Isotretinoin plus ch14.18, GM-CSF and IL-2 | Isotretinoin alone | Effect |
|---|---|---|---|---|
| EFSITT (226 eligible randomised patients)Event-free survival from randomisation | primarymedian follow-up 2.1 yearsYu 2010 | 66% at 2 y | 46% at 2 y | P=0.01Kaplan-Meier estimates reported as 66±5% vs 46±5% (± standard error). The study met its criteria for early stopping for efficacy with 61% of the expected events observed. |
| OSITT (226 eligible randomised patients) | primarymedian follow-up 2.1 yearsYu 2010 | 86% at 2 y | 75% at 2 y | P=0.02Estimates reported as 86±4% vs 75±5% (± standard error); the P value is stated in the abstract to be without adjustment for interim analyses. |
| EFSEligible randomised patients (226; 114 immunotherapy, 112 isotretinoin alone)Event-free survival from randomisation | long term-updateYu 2021 | 56.6% at 5 y | 46.1% at 5 y | P=0.042Reported as 56.6±4.7% vs 46.1±5.1% (± standard error). Arm sizes in this report (114 and 112) differ from the 2010 report (113 and 113). |
| OSEligible randomised patients (226; 114 immunotherapy, 112 isotretinoin alone) | long term-updateYu 2021 | 73.2% at 5 y | 56.6% at 5 y | P=0.045Reported as 73.2±4.2% vs 56.6±5.1% (± standard error). |
| Endpoint | Analysis | Isotretinoin plus ch14.18, GM-CSF and IL-2 | Isotretinoin alone | Effect |
|---|---|---|---|---|
| EFSITT (226 eligible randomised patients)Event-free survival from randomisation | primarymedian follow-up 2.1 yearsYu 2010 | 66% at 2 y | 46% at 2 y | P=0.01Kaplan-Meier estimates reported as 66±5% vs 46±5% (± standard error). The study met its criteria for early stopping for efficacy with 61% of the expected events observed. |
| OSITT (226 eligible randomised patients) | primarymedian follow-up 2.1 yearsYu 2010 | 86% at 2 y | 75% at 2 y | P=0.02Estimates reported as 86±4% vs 75±5% (± standard error); the P value is stated in the abstract to be without adjustment for interim analyses. |
| EFSEligible randomised patients (226; 114 immunotherapy, 112 isotretinoin alone)Event-free survival from randomisation | long term-updateYu 2021 | 56.6% at 5 y | 46.1% at 5 y | P=0.042Reported as 56.6±4.7% vs 46.1±5.1% (± standard error). Arm sizes in this report (114 and 112) differ from the 2010 report (113 and 113). |
| OSEligible randomised patients (226; 114 immunotherapy, 112 isotretinoin alone) | long term-updateYu 2021 | 73.2% at 5 y | 56.6% at 5 y | P=0.045Reported as 73.2±4.2% vs 56.6±5.1% (± standard error). |
Appears in
Sources
Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363(14):1324-34.
Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, et al. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021;27(8):2179-2189.