title: A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials.
abstract: Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled. Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. No stopping rules were met. Main adverse events (AEs) were grades 1 and 2 gastrointestinal toxicities. In view of these results, we expanded the study and treated 79 additional patients: 27 with azacitidine (AZA) and 52 with azacitidine and vorinostat (AZA+V). Median follow-up was 22.7 months (12.6-47.5). Sixty-day survival rate was 79% (AZA=67%, AZA+V=85%, P=0.07). Median overall survival was 7.6 months (4.5-10.7). Median event-free survival was 4.5 months (3.5-5.6). Main AEs included grades 1 and 2 gastrointestinal toxicities. Our results suggest this subset of patients can be safely treated within clinical trials and derive clinical benefit. Relaxation of standard exclusion criteria may increase the pool of patients likely to benefit from therapy.
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G
authors: G
authors: Montalban-Bravo
authors: Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors: X
authors: X
authors: Huang
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: K
authors: K
authors: Naqvi
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: E
authors: E
authors: Jabbour
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G
authors: G
authors: Borthakur
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: C D
authors: CD
authors: DiNardo
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: N
authors: N
authors: Pemmaraju
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: J
authors: J
authors: Cortes
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Verstovsek
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: T
authors: T
authors: Kadia
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: N
authors: N
authors: Daver
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: W
authors: W
authors: Wierda
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Y
authors: Y
authors: Alvarado
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M
authors: M
authors: Konopleva
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: F
authors: F
authors: Ravandi
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z
authors: Z
authors: Estrov
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: N
authors: N
authors: Jain
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: A
authors: A
authors: Alfonso
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M
authors: M
authors: Brandt
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: T
authors: T
authors: Sneed
authors: Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors: H-C
authors: HC
authors: Chen
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: H
authors: H
authors: Yang
authors: Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors: C
authors: C
authors: Bueso-Ramos
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Pierce
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: E
authors: E
authors: Estey
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z
authors: Z
authors: Bohannan
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: H M
authors: HM
authors: Kantarjian
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G
authors: G
authors: Garcia-Manero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers