Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects With HR First Relapse B-precursor ALL
Phase 3N = 108NCT02393859
- Population
- Children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow) or with M2 marrow at randomization; 108 randomized
- Design
- Randomized phase 3 trial at 47 centers in 13 countries; patients enrolled November 2015 to July 2019 (data cutoff 17 July 2019). Third consolidation was 1 cycle of blinatumomab (15 µg/m2/d continuous intravenous infusion for 4 weeks) or consolidation chemotherapy, before allogeneic hematopoietic stem cell transplant. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. Amgen study number 20120215 (the organisation study ID on ClinicalTrials.gov and the name used in the FDA multidisciplinary review of 20 June 2023).
- Primary endpoint
- EFS
- Arms
- Blinatumomab consolidation (experimental, n = 54): 1 cycle of blinatumomab, 15 µg/m2/d continuous intravenous infusion for 4 weeks, as third consolidation
- Chemotherapy consolidation (control, n = 54): Consolidation chemotherapy as third consolidation
- People
- Locatelli F, senior author von Stackelberg A
EFSHR 0.33 (95% CI 0.18–0.61)OSHR 0.43 (95% CI 0.18–1.01)Δ MRD-negative remission rate+36 points
Show the numbers
| Endpoint | Analysis | Blinatumomab consolidation | Chemotherapy consolidation | Effect |
|---|---|---|---|---|
| EFSAll randomized patients (108)Event-free survival; events were relapse, death, second malignancy, or failure to achieve complete remission | primarymedian follow-up 22.4 monthsLocatelli 2021 | — | — | HR 0.33 (95% CI 0.18–0.61)P<0.001Incidence of events 31% with blinatumomab vs 57% with chemotherapy (an event incidence, not an EFS probability); log-rank P < .001; interquartile range of follow-up 8.1 to 34.2 months. Enrollment ended early for benefit under a prespecified stopping rule. |
| OSAll randomized patients (108)Overall survival (key secondary end point) | primarymedian follow-up 22.4 monthsLocatelli 2021 | — | — | HR 0.43 (95% CI 0.18–1.01)Deaths in 8 patients (14.8%) with blinatumomab and 16 (29.6%) with chemotherapy; the interval includes 1. |
| MRD-negative remission ratePatients with MRD assessment (49 with blinatumomab, 48 with chemotherapy)Minimal residual disease remission (secondary end point) | primaryLocatelli 2021 | 90% | 54% | 44 of 49 vs 26 of 48; difference 35.6% (95% CI 15.6% to 52.5%). |
| Endpoint | Analysis | Blinatumomab consolidation | Chemotherapy consolidation | Effect |
|---|---|---|---|---|
| EFSAll randomized patients (108)Event-free survival; events were relapse, death, second malignancy, or failure to achieve complete remission | primarymedian follow-up 22.4 monthsLocatelli 2021 | — | — | HR 0.33 (95% CI 0.18–0.61)P<0.001Incidence of events 31% with blinatumomab vs 57% with chemotherapy (an event incidence, not an EFS probability); log-rank P < .001; interquartile range of follow-up 8.1 to 34.2 months. Enrollment ended early for benefit under a prespecified stopping rule. |
| OSAll randomized patients (108)Overall survival (key secondary end point) | primarymedian follow-up 22.4 monthsLocatelli 2021 | — | — | HR 0.43 (95% CI 0.18–1.01)Deaths in 8 patients (14.8%) with blinatumomab and 16 (29.6%) with chemotherapy; the interval includes 1. |
| MRD-negative remission ratePatients with MRD assessment (49 with blinatumomab, 48 with chemotherapy)Minimal residual disease remission (secondary end point) | primaryLocatelli 2021 | 90% | 54% | 44 of 49 vs 26 of 48; difference 35.6% (95% CI 15.6% to 52.5%). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.33 | 0.18–0.61 |
| OS | 0.43 | 0.18–1.01 |