Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Brunner Andrew M, Blonquist Traci M, DeAngelo Daniel J, McMasters Malgorzata, Fell Geoffrey, Hermance Nicole M, Winer Eric S, Lindsley R Coleman, Hobbs Gabriela S, Amrein Philip C, Hock Hanno R, Steensma David P, Garcia Jacqueline S, Luskin Marlise R, Stone Richard M, Ballen Karen K, Rosenblatt Jacalyn, Avigan David, Nahas Myrna R, Mendez Lourdes M, McAfee Steven L, Moran Jenna A, Bergeron Meghan, Foster Julia, Bertoli Christina, Manning Amity L, McGregor Kristin L, Fishman Kaitlyn M, Kuo Frank C, Baltay Michele T, Macrae Molly, Burke Meghan, Behnan Tanya, Wey Margaret C, Som Tina T, Ramos Aura Y, Rae Jessica, Lombardi Story Jennifer, Nelson Nicole, Logan Emma, Connolly Christine, Neuberg Donna S, Chen Yi-Bin, Graubert Timothy A, Fathi Amir T
Аннотация
METHODS: We did a single-arm, phase 2 trial of patients recruited from the Dana-Farber/Harvard Cancer Center in the USA. Eligible patients had previously untreated acute myeloid leukaemia, an Eastern Cooperative Oncology Group performance status of 0-2, and were at high risk of disease as defined by the presence of an adverse-risk karyotype, the presence of secondary acute myeloid leukaemia arising from previous myelodysplastic syndrome or myeloproliferative neoplasm, the presence of therapy-related acute myeloid leukaemia, or being 65 years or older. Enrolled patients received 7 + 3 induction chemotherapy of continuous infusion of cytarabine (100 mg/m2 per day on days 1-7) and intravenous bolus of idarubicin (12 mg/m2 per day on days 1-3). Oral alisertib (30 mg) was given twice per day on days 8-15. Patients could receive up to four consolidation cycles with cytarabine and alisertib, and alisertib maintenance for 12 months. The primary endpoint was a composite including the proportion of patients achieving complete remission and those with a complete remission with incomplete neutrophil or platelet count recovery. Analyses were per-protocol. This study is registered with Clinicaltrials.gov, number NCT02560025, and has completed enrolment.
FINDINGS: Between Dec 31, 2015, and Aug 1, 2017, we enrolled a total of 39 eligible patients. 19 (49%) of 39 patients had secondary acute myeloid leukaemia and three (8%) had therapy-related acute myeloid leukaemia. At mid-induction, 33 (85%) of 39 patients showed marrow aplasia, six (15%) received re-induction. The median follow-up was 13·7 months (IQR 12·7-14·4). Composite remission was 64% (two-stage 95% CI 48-79), with 20 (51%) of 39 patients achieving complete remission and five (13%) achieving complete remission with incomplete neutrophil or platelet count recovery. The most common grade 3 or 4 adverse events included febrile neutropenia (16 [41%] of 39), neutropenia (12 [31%]), thrombocytopenia (13 [33%]), anaemia (11 [28%]), anorexia (nine [23%]), and oral mucositis (four [10%]). No treatment-related deaths were observed.
INTERPRETATION: These results suggest that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. This study met criteria to move forward to a future randomised trial.
FUNDING: Millennium Pharmaceuticals.