CPX-351: A Randomized Phase 2b Study of CPX-351 v. Intensive Salvage Therapy in '65 Yo First Relapse AML Patients: Initial Efficacy and Safety Report
Notice bibliographique
Résumé
Abstract Abstract 254 Background: CPX-351 is a liposomal formulation containing a 5:1 molar ratio of cytarabine (Ara-C) and daunorubicin (DNR) shown to maximize anti-tumor synergy. Preclinical studies demonstrated accumulation of CPX-351 within bone marrow with preferential uptake of liposomes by leukemia cells. A Phase 1 study using 90-minute I.V. infusions on Days 1, 3, and 5 found the MTD to be 101 u/m2 (1 u = 1 mg Ara-C + 0.44 mg DNR) and demonstrated marked prolongation of plasma Ara-C and DNR half-life. Eighteen of the 45 AML patients were in 1st relapse with 8 patients <65 years of age. All 8 achieved aplasia and 4/8 achieved CR after CPX-351. (Feldman E, et al. Blood 2008;112:Abst 2984). On this basis, a randomized Phase 2b study was initiated in first relapse AML patients comparing CPX-351 against investigator's choice of salvage regimen. This report summarizes initial safety and response data for patients randomized and followed >60 days. Methods: Patients ≤65yo with AML in 1st relapse after an initial CR lasting >1 month with ECOG PS= 0–2, SCr < 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT/AST < 3 × ULN, and LVEF > 50% were eligible. Patients were randomized 2:1 to receive CPX-351 (100 u/m2; D 1, 3, 5) or investigators choice of intensive salvage treatment. Up to 2 inductions and 2 consolidation courses were allowed. Post remission treatment with hematopoietic stem cell transplantation (HSCT) was permitted. Patients were stratified using the European Prognostic Index (EPI) (Breems DA, et al. J Clin Oncol, 2005 Mar 20;23:1969–1978). The primary efficacy endpoint is % survival at 1-year and 2° efficacy endpoints include CR+ CRi rate, CR+ CRi duration, EFS, aplasia rate (<5% blasts + <20% cellularity), and % referred for HSCT. Deaths at Day 30 and 60 and SAE frequency were monitored. Results: As of November 12, 2010, 126 patients were accrued at 35 of 46 sites in the US, Canada, France and Poland. 94% had received prior anthracycline therapy. Most patients had a single induction (88% v. 93%) and salvage consisted mostly of MEC (51%) or 7+3 (16%). Demographic and EPI risk factors were well balanced except for prior HSCT (27% (CPX-351) vs. 18% (7+3)). Compared to control, CPX-351 had greater anti-leukemia activity based on rate of aplasia (90% vs. 60%) and CR + CRi rate (51% vs. 42%). A greater response improvement with CPX-351 vs. control was observed in the EPI unfavorable group (23/56 (41.1%) vs. 9/30 (30%))as well as in patients with no history of prior HSCT (56% vs. 41%). Early deaths ( Conclusion: In this Phase 2b randomized trial, CPX-351 has substantial clinical activity and is safe compared to salvage therapy. Improved efficacy was observed in patients with unfavorable EPI scores and in those with no history of HSCT. Longer myelosuppression with CPX-351 led to increased febrile neutropenia and infections. These initial data support further investigation of CPX-351 in first relapse AML patients. This study is expected to be completed in November 2011 and final results (including EFS + OS analyses) will be available at that time. Disclosures: Cortes: Celator: Membership on an entity's Board of Directors or advisory committees. Paulsen:Celator Pharmaceuticals: Employment. Louie:Celator: Employment.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».