Phase 2 open-label study of MEDI-551 and bendamustine versus rituximab and bendamustine in adults with relapsed or refractory CLL.
Bibliographic record
Abstract
3028 Background: Patients (pts) with relapsed/refractory (RR) chronic lymphocytic leukemia (CLL) need therapies that induce prolonged disease control. MEDI-551, an affinity-optimized anti-CD19 antibody, destroys CLL cells by antibody-dependent cellular cytotoxicity. A phase 2 randomized, open-label study (NCT01466153) is evaluating the clinical activity and safety/tolerability of 2 doses of MEDI-551 + bendamustine compared to rituximab + bendamustine in RR CLL patients. Methods: Pts were initially randomized to receive bendamustine + MEDI-551 2 or 4 mg/kg or rituximab (R). Safety assessments include adverse events (AEs) and laboratory parameters. Disease response was determined using 2008 International Working Group criteria. Results: The safety population comprised 124 pts across all arms. Median age was 66y (range 41–81); with deletion (del) (17p): 9%, del (11q): 22%, del (13q): 31%, trisomy 12: 11%. Median number of treatment cycles: 4 (range 1–6). The most common (≥20%) treatment-related AEs with MEDI-551 were infusion-related reaction (IRR), fatigue and nausea; neutropenia and nausea were most common with R; most treatment-related AEs were grade 1/2; grade 3/4 treatment-related AEs are listed in Table 1. 20% of pts receiving MEDI-551and 18% patients receiving R discontinued treatment due to AEs. An interim analysis of the MEDI-551-treated pts (25 per arm) showed response rates of 48 vs. 64% in the 2 vs. 4 mg/kg arms. Conclusions: MEDI-551 in combination with bendamustine has a manageable toxicity profile that appears to be different compared to rituximab in RR CLL patients. MEDI-551 dosed at 4 mg/kg as compared to 2 mg/kg may have a greater efficacy without any increase in toxicity. Clinical trial information: NCT01466153. Treatment-related grade 3/4 AEs (≥5% of patients). MEDI-551 Rituximab n (%) 2 mg/kg (n=33) 4 mg/kg (n=44) (n=47) Pts reporting ≥1 event 18 (55) 16 (36) 21 (45) Neutropenia 6 (18) 4 (9) 11 (23) Febrile neutropenia 0 1 (2) 5 (11) Thrombocytopenia 0 1 (2) 5 (11) IRR 6 (18) 4 (9) 1 (2) Decreased neutrophils 1 (3) 2 (5) 3 (6) Cytokine release syndrome 2 (6) 0 0 Tumor lysis syndrome 0 2 (5) 0
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".