AALL1331
Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Phase 3N = 208NCT02101853
- Population
- Patients aged 1 to 30 years with first relapse of B-ALL at high or intermediate risk, excluding Down syndrome, Philadelphia chromosome-positive ALL, prior hematopoietic stem cell transplant and prior blinatumomab; 208 randomized
- Design
- Randomized phase 3 trial of the Children's Oncology Group at 155 hospitals in the US, Canada, Australia and New Zealand; 669 patients enrolled from December 2014 to September 2019. All received 4-week reinduction chemotherapy, then randomization to 2 cycles of blinatumomab or 2 cycles of multiagent chemotherapy, each followed by transplant. Randomization was terminated at the recommendation of the data and safety monitoring committee without meeting stopping rules for efficacy or futility; 80 of 131 planned events had occurred. The significance threshold was a 1-sided P < .025.
- Primary endpoint
- DFS
- Arms
- Blinatumomab consolidation (experimental, n = 105): 2 cycles of blinatumomab after reinduction, followed by transplant
- Chemotherapy consolidation (control, n = 103): 2 cycles of multiagent chemotherapy after reinduction, followed by transplant
- People
- Brown PA, senior author Loh ML, Children's Oncology Group
DFSHR 0.70 (95% CI 0.47–1.03)Δ 24-month DFS+15.4 pointsOSHR 0.62 (95% CI 0.39–0.98)Δ 24-month OS+12.9 points
Show the numbers
| Endpoint | Analysis | Blinatumomab consolidation | Chemotherapy consolidation | Effect |
|---|---|---|---|---|
| DFSRandomized patients (208)Disease-free survival from randomization | primarymedian follow-up 2.9 yearsBrown 2021 | 54.4% at 2 y | 39% at 2 y | HR 0.70 (95% CI 0.47–1.03)P=0.03 (1-sided)Hazard ratio for disease progression or mortality. Pre-specified significance threshold was 1-sided P < .025, so the difference was not statistically significant; randomization ended early with 80 of 131 planned events. Data cutoff is the end of follow-up stated in the abstract (30 September 2020). |
| OSRandomized patients (208)Overall survival from randomization (secondary end point) | primarymedian follow-up 2.9 yearsBrown 2021 | 71.3% at 2 y | 58.4% at 2 y | HR 0.62 (95% CI 0.39–0.98)P=0.02 (1-sided)Hazard ratio for mortality; secondary end point. |
| Endpoint | Analysis | Blinatumomab consolidation | Chemotherapy consolidation | Effect |
|---|---|---|---|---|
| DFSRandomized patients (208)Disease-free survival from randomization | primarymedian follow-up 2.9 yearsBrown 2021 | 54.4% at 2 y | 39% at 2 y | HR 0.70 (95% CI 0.47–1.03)P=0.03 (1-sided)Hazard ratio for disease progression or mortality. Pre-specified significance threshold was 1-sided P < .025, so the difference was not statistically significant; randomization ended early with 80 of 131 planned events. Data cutoff is the end of follow-up stated in the abstract (30 September 2020). |
| OSRandomized patients (208)Overall survival from randomization (secondary end point) | primarymedian follow-up 2.9 yearsBrown 2021 | 71.3% at 2 y | 58.4% at 2 y | HR 0.62 (95% CI 0.39–0.98)P=0.02 (1-sided)Hazard ratio for mortality; secondary end point. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.7 | 0.47–1.03 |
| OS | 0.62 | 0.39–0.98 |
Appears in
Sources
Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):833-842.