A randomized, double-blind, placebo-controlled phase 3 study of ibrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in subjects with newly diagnosed nongerminal center B-cell subtype of diffuse large B-cell lymphoma (DLBCL).
Bibliographic record
Abstract
TPS8615^ Background: The standard regimen for frontline treatment of DLBCL is R-CHOP, which results in a complete response (CR) in 76% of patients and a 10-year overall survival (OS) rate of 44%. DLBCL can be classified by immunohistochemistry (IHC) into 2 subgroups: germinal center B-cell-like (GCB) or non-GCB (including the activated B-cell-like and some intermediate molecular subtypes). Prognosis is suggested to be least favorable for non-GCB DLBCL, the subgroup associated with NF-κB pathway activation and chronic active B-cell receptor (BCR) signaling. Ibrutinib inhibits BCR signaling by covalently binding to Bruton's tyrosine kinase. A phase 2 monotherapy study in relapsed/refractory DLBCL showed a 41% overall response rate (ORR) in the non-GCB subgroup (ASH 2012). A phase 1 study combining ibrutinib with R-CHOP showed an ORR of 100% in DLBCL and a favorable safety profile (ASH 2013), suggesting that ibrutinib can be safely combined with R-CHOP. Methods: The PHOENIX study, PCI32765DBL3001, is a phase 3 randomized, placebo-controlled, double-blind study of ibrutinib in combination with R-CHOP versus R-CHOP for the treatment of newly diagnosed non-GCB DLBCL. The study aims to enroll 800 patients (≈400 per arm). All patients will receive standard doses of R-CHOP therapy for 6 or 8 cycles (according to local practice), with ibrutinib 560 mg daily or placebo. The primary objective is to evaluate if the addition of ibrutinib to R-CHOP will result in prolongation of event-free survival. Secondary objectives include progression-free survival, OS, ORR (CR + PR), CR rate, and safety. The study will enroll previously untreated adult patients with the non-GCB subgroup of DLBCL determined by central IHC (Hans algorithm). Key exclusion criteria include central nervous system involvement or primary mediastinal lymphoma, diagnosis or treatment for malignancy other than DLBCL, or history of indolent lymphoma. Approximately 280 sites globally will enroll patients. Enrollment began in Q4 of 2013. Clinical trial information: NCT01855750.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
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".