Bortezomib reinduction therapy to improve response rates in pediatric ALL in first relapse: A Children’s Oncology Group (COG) study (AALL07P1).
Bibliographic record
Abstract
10003 Background: Bortezomib (bortez) is a reversible inhibitor of the 26S proteasome. Promising results have been reported adding bortezomib to reinduction chemotherapy in patients (pts) with ALL in 2nd or later relapse (Messinger, Blood 2012). Methods: This was a phase 2 study of bortez with reinduction chemotherapy in 1st relapse pediatric ALL that enrolled pts with pre-B ALL (relapse <36 months (m) from diagnosis). This report summarizes results from 61 evaluable pre-B ALL pts ≤21 yrs old, either <18m (stratum 1) or 18-36m (stratum 2) from diagnosis. Therapy consisted of bortez (1.3 mg/m2, days 1, 4, 8, and 11) with reinduction chemotherapy (vincristine, prednisone, PEG-asparaginase, doxorubicin). Complete response (CR2) rates and minimal residual disease (MRD) were determined at the end of the first 5-week therapy block. AALL07P1 utilized a stratified 2-stage design (London 2005) with the primary objective of comparing CR2 rates at the end of block 1 of therapy to historical control CR2 rates (AALL01P2). Block 2 included cyclophosphamide, etoposide, and bortez followed by 5g/m2 methotrexate. Biology studies included assessment of NF-κB activity. Results: 61 evaluable pre-B ALL pts were assessed. Toxicities were similar to AALL01P2, including 10 Grade 3- 4 hypotension, 4 Grade 4 hypertriglyceridemia, 3 Grade 3-4 typhlitis, and 2 Grade 3-4 enterocolitis. There were 2 deaths due to infection. Although Grade 3-4 infections were not infrequent (13 in block 1 and 7 in block 2) there were no reports of respiratory distress syndrome or Grade 4 peripheral neuropathy. 42 of the 61 patients enrolled (18/28 (64%) in Stratum 1 and 24/33 (73%) in stratum 2) attained CR2 at the end of Induction I. Based on CR2 response rate compared to historical controls, the study met its primary response objective. The number of pts in CR2 with MRD <0.1% also improved from AALL01P2; among pts achieving CR2, MRD was <0.1% in 41% (16/39) in AALL01P2 vs. 71% (25/35) (p= 0.073, Fisher’s exact test). Conclusions: Based on response rates in the very early and early first relapse pre-B ALL, AALL07P1 met its predefined efficacy benchmark. We conclude that bortezomib is worthy of further study in pediatric ALL. Clinical trial information: NCT00873093.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".