Tailor: Interventional Study Evaluating Physician's Choice of Ibrutinib Monotherapy or Ibrutinib-Venetoclax Combination Using Dose Modifications and Alternate Dosing Approaches in Patients with Untreated Chronic Lymphocytic Leukemia
Notice bibliographique
Résumé
Background: Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) that has changed the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) with durable responses and improved overall survival (OS). In the pivotal Phase 3 GLOW and Phase 2 CAPTIVATE trials, fixed-duration combination of ibrutinib-venetoclax (I+V) resulted in deep and sustained clinical responses, and a broadly manageable safety profile in patients with CLL. Several factors including genetic features, disease status, comorbidities, patient preferences, and safety profiles contribute to selection of the optimal therapeutic option for patients with CLL in the first-line setting. Adverse events (AEs), such as atrial fibrillation, bleeding, and hypertension, have been seen with the BTKi therapeutic class.Long-term clinical and real-world experience with ibrutinib has led to specific guidance regarding AE management, which has been included in the updated ibrutinib prescribing information (US PI, May 2022; EU SmPC, April 2023). Retrospective evidence, including post-hoc analyses of clinical trial data, demonstrates that dose reduction of ibrutinib mitigates recurrence or worsening of AEs while preserving efficacy. Thus, these findings together support the rationale to prospectively evaluate the impact of regimen and dosing flexibility of ibrutinib in patients with untreated CLL. Aim: The key objective of the TAILOR study (NCT05963074) is to assess the efficacy and safety of I+V and ibrutinib monotherapy regimens with both a proactive and reactive dose adjustment in patients with untreated CLL. Methods: TAILOR is a phase 2, two-arm, four-cohort interventional study designed to provide physicians the choice of ibrutinib monotherapy or I+V combination therapy for previously untreated patients with CLL and prospectively evaluate proactive and reactive dose adjustment approaches. Eligible patients will have previously untreated active CLL, needing therapy as per iwCLL 2018 criteria. Key exclusion criteria include significant active or history of cardiovascular disease, uncontrolled hypertension, and ECOG performance status > 2. Patients will be randomized after selection of regimen: I+V fixed-duration regimen (2 cohorts, 80 patients in each cohort) or ibrutinib monotherapy (2 cohorts, 80 patients in each cohort), as per physician's choice. Patients in the I+V arm will receive ibrutinib 420 mg QD as lead-in for 3 cycles plus 12 cycles of either ibrutinib 420 mg QD (Cohort 1a) or 280 mg QD (Cohort 1b) in combination with venetoclax, which will be initiated in cycle 4 with dose ramp-up per label over 5 weeks (20, 50, 100, 200, and 400 mg/day) and continued at 400 mg/day dose from cycle 5 onward. In addition, patients with deletion 17p and/or mutated TP53 will receive optional ibrutinib maintenance. Patients in the ibrutinib monotherapy arm will receive ibrutinib 420 mg QD (Cohort 2a) or 420 mg QD for 3 cycles, then 280 mg QD (Cohort 2b) until progressive disease or unacceptable toxicity ( Figure). All cohorts will follow the dose modification guidance as per protocol based on the US PI/ EU SmPC. The primary endpoint is best overall response rate as assessed by investigators and compared with historic controls. Secondary endpoints include: complete response rate, duration of response, PFS, and OS; undetectable minimal residual disease rate (I+V cohorts only); safety (AEs, discontinuation due to AEs, adherence rates); and patient reported outcomes. The study is currently recruiting patients.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».