ANBL1221
A Phase II Randomized Trial of Irinotecan/Temozolomide With Temsirolimus or Chimeric 14.18 Antibody in Children With Refractory, Relapsed or Progressive Neuroblastoma
Phase 2N = 36NCT01767194
- Population
- Patients of any age at first relapse, progression or refractory disease; 36 enrolled and 35 eligible in the randomised phase (February 2013 to March 2015).
- Design
- Open-label, randomised phase 2 selection design (Children's Oncology Group): irinotecan and temozolomide with either temsirolimus or dinutuximab plus GM-CSF, 1:1, 21-day cycles up to 17 cycles. Primary endpoint objective response by central review after six cycles. A later report added a non-randomised expansion cohort receiving irinotecan-temozolomide-dinutuximab-GM-CSF.
- Primary endpoint
- ORR
- Arms
- Irinotecan-temozolomide plus temsirolimus (experimental, n = 18): Temozolomide 100 mg/m2 and irinotecan 50 mg/m2 on days 1-5 with temsirolimus 35 mg/m2 on days 1 and 8, 21-day cycles
- Irinotecan-temozolomide plus dinutuximab and GM-CSF (experimental, n = 17): Irinotecan and temozolomide as above with dinutuximab on days 2-5 and GM-CSF on days 6-12, 21-day cycles
- Expansion cohort, irinotecan-temozolomide-dinutuximab-GM-CSF (experimental, n = 36): Irinotecan, temozolomide, dinutuximab and GM-CSF, non-randomised expansion cohort (August 2016 to May 2017)
- All patients on irinotecan-temozolomide-dinutuximab-GM-CSF (experimental, n = 53): The 17 randomised and 36 expansion patients who received irinotecan, temozolomide, dinutuximab and GM-CSF (as pooled in the 2020 report)
- People
- Mody R, senior author Bagatell R, Children's Oncology Group
Show the numbers
| Endpoint | Analysis | Irinotecan-temozolomide plus temsirolimus / Irinotecan-temozolomide plus dinutuximab and GM-CSF / Expansion cohort, irinotecan-temozolomide-dinutuximab-GM-CSF / All patients on irinotecan-temozolomide-dinutuximab-GM-CSF | Control | Effect |
|---|---|---|---|---|
| ORREligible randomised patients (35); ITTObjective (complete or partial) response by central review after six cycles | primarymedian follow-up 1.26 yearsMody 2017 | 6% (0.0–16.1%) | — | 1 of 18 (partial response) with temsirolimus; 9 of 17 (4 partial, 5 complete responses) with dinutuximab. Selection design: no arm served as a control and the trial was not designed to compare the arms formally. |
| ORRNon-randomised expansion cohort (36 patients), intention to treatObjective (complete or partial) response by the International Neuroblastoma Response Criteria | primaryMody 2020 | 36.1% (20.4–51.8%) | — | 13 of 36 patients. |
| ORRAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 41.5% (28.2–54.8%) | — | 22 of 53 patients; stable disease was also observed in 22 of 53. Pooled randomised and expansion patients as reported by the authors. |
| PFSAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 67.9% at 12 mo (55.4–80.5%) | — | Reported as 67.9% ± 6.4% (± standard error) with the 95% CI shown. |
| OSAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 84.9% at 12 mo (75.3–94.6%) | — | Reported as 84.9% ± 4.9% (± standard error) with the 95% CI shown. |
| Endpoint | Analysis | Irinotecan-temozolomide plus temsirolimus / Irinotecan-temozolomide plus dinutuximab and GM-CSF / Expansion cohort, irinotecan-temozolomide-dinutuximab-GM-CSF / All patients on irinotecan-temozolomide-dinutuximab-GM-CSF | Control | Effect |
|---|---|---|---|---|
| ORREligible randomised patients (35); ITTObjective (complete or partial) response by central review after six cycles | primarymedian follow-up 1.26 yearsMody 2017 | 6% (0.0–16.1%) | — | 1 of 18 (partial response) with temsirolimus; 9 of 17 (4 partial, 5 complete responses) with dinutuximab. Selection design: no arm served as a control and the trial was not designed to compare the arms formally. |
| ORRNon-randomised expansion cohort (36 patients), intention to treatObjective (complete or partial) response by the International Neuroblastoma Response Criteria | primaryMody 2020 | 36.1% (20.4–51.8%) | — | 13 of 36 patients. |
| ORRAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 41.5% (28.2–54.8%) | — | 22 of 53 patients; stable disease was also observed in 22 of 53. Pooled randomised and expansion patients as reported by the authors. |
| PFSAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 67.9% at 12 mo (55.4–80.5%) | — | Reported as 67.9% ± 6.4% (± standard error) with the 95% CI shown. |
| OSAll patients receiving irinotecan-temozolomide-dinutuximab-GM-CSF (53) | primaryMody 2020 | 84.9% at 12 mo (75.3–94.6%) | — | Reported as 84.9% ± 4.9% (± standard error) with the 95% CI shown. |
Appears in
Sources
Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017;18(7):946-957.
Mody R, Yu AL, Naranjo A, Zhang FF, London WB, Shulkin BL, et al. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol. 2020;38(19):2160-2169.