CANADIAN CANCER TRIALS GROUP (CCTG) LY.17: A RANDOMIZED PHASE II STUDY EVALUATING NOVEL SALVAGE THERAPY PRE‐AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (RR‐DLBCL) ‐ OUTCOME OF IBRUTINIB + R‐GDP
Bibliographic record
Abstract
Introduction: Salvage chemotherapy and ASCT remains the standard of care in patients (pts) with relapsed/refractory (RR) DLBCL. CCTG trial LY.12 established rituximab combined with gemcitabine, dexamethasone and cisplatin (R-GDP) as a standard of care in this population (Crump JCO 2014), with a low incidence of febrile neutropenia (12%) and infection. Methods: CCTG LY.17 is an ongoing multi-arm randomized phase II “pick a winner” trial evaluating novel salvage therapy and R-GDP in RR-DLBCL pts post rituximab and anthracycline based chemotherapy failure. The first experimental arm evaluated ibrutinib 560 mg PO daily d1-21 with R-GDP (IR-GDP) q3W. Primary endpoint of the study is overall response rate (ORR) after 3 cycles of therapy using CT imaging (FDG-PET response is an exploratory endpoint). According to the protocol futility rule, any treatment arm with an ORR lower than the control arm at the first interim analysis (n = 16) is not considered worthy of further testing and enrolment in that arm will cease. After the run-in cohort of the first 5 IR-GDP pts suggested an increased risk of infection, twice weekly blood count monitoring and antimicrobial prophylaxis for opportunistic infection was recommended along with consideration of G-CSF support. This report is the result of the first interim analysis reporting on 30 pts. Results: Baseline pt characteristics are reported in Table 1. In the IR-GDP arm 11/14 pts received an ibrutinib dose intensity of >90%. The ORR to IR-GDP was 28.6% (CR 0, PR 28.6%, SD 28.6%, PD 14.3%, inevaluable 28.6%). 8 SAEs including 2 grade 5 events (1 sepsis, 1 pneumonia) and 3 grade 3 infectious events were reported in the IR-GDP arm. Median neutrophil and lymphocyte counts were 1.75 (0.9-20.7) and 0.23 (0.15-0.3) at time of onset of infection. The ORR to R-GDP was 50.1% (CR 6.3%, PR 43.8%, SD 12.5%, PD 37.5%, inevaluable 0). Among patients assigned to R-GDP there were no infections grade 3 or higher; there were 4 SAEs and no grade 5 events. At the time of database lock (median f/u 3.5 months, range 0.7-9.2), all patients were off protocol treatment (IR-GDP:R-GDP; death 2:0;, AE 1:0, PD prior to completion of protocol therapy 1:4; patient choice 0:1 and treatment complete 10:11) with 19 pts having a progression event (IR-GDP:R-GDP; on treatment 3:3; during follow-up 5:5; death without PD 2:1) and 11 alive without PD (IR-GDP 4, R-GDP 7). Conclusions: Addition of ibrutinib did not improve the activity of R-GDP and appeared to be associated with increased risk of infection; accrual to this arm has ceased and additional combinations are being explored. Keywords: diffuse large B-cell lymphoma (DLBCL); ibrutinib; salvage treatment.
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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 | 0.012 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 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".