162 A phase II study of decitabine in advanced chronic myelomonocytic leukemia (CMML)

2011 ◽  
Vol 35 ◽  
pp. S63-S64
Author(s):  
T. Braun ◽  
N. Droin ◽  
R. Itzykson ◽  
B. de Renzis ◽  
F. Dreyfus ◽  
...  
2016 ◽  
Vol 57 (10) ◽  
pp. 2441-2444 ◽  
Author(s):  
Srinivas K. Tantravahi ◽  
Philippe Szankasi ◽  
Jamshid S. Khorashad ◽  
Kim-Hien Dao ◽  
Tibor Kovacsovics ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4903-4903
Author(s):  
Gautam Borthakur ◽  
Hagop Kantarjian ◽  
Elihu Estey ◽  
Srdan Verstovsek ◽  
Guillermo Garcia-Manero ◽  
...  

Abstract Homoharringtonine (HHT) is a plant alkaloid that inhibits protein synthesis, induces differentiation and apoptosis of myeloid cells. We initiated a phase II study of intra-venous HHT in patients (pts) diagnosed with MDS by WHO criteria to assess safety and efficacy of HHT in this setting. Responses were recorded according to the MDS response criteria defined by NCI working group. Pts received HHT 2.5 mg/m2 by continuous 24-hour intravenous infusion daily for 7 days every 4 weeks until a) a complete remission (CR) was achieved, or b) failure to achieve a CR after 3 courses of therapy or c) unacceptable toxicities developed. The dose was increased to 3.0 mg/m2 for pts with no response after the 1st course. Nine pts have been enrolled (6 male and 3 female). Median age was 70 yrs (range 55 to 84 yrs) and 4 pts had secondary MDS. Four pts had refractory anemia with excess blasts-1 (RAEB-1), 3 had RAEB-2, 1 had chronic myelomonocytic leukemia (CMML-1) and 1 had MDS/myeloproliferative disorder (MDS/MPD). IPSS score was intermediate-1 in 1 pt, intermediate-2 in 7 pts and high in 1 pt. Seven pts (78%) received only one cycle of HHT. One (11%) pt had a CR (including cytogenetic CR) that lasted for 67 days, 5 pts discontinued treatment due to lack of response and1 pt with stable disease decided to withdraw from the study. After a median follow-up of 54 days (range, 37 to 145 days) 2 pts have died, one on day 37 due to intracranial bleed secondary to thrombocytopenia and one on day 39 due to invasive fungal infection. Grade 2 toxicities included fatigue (4 pts), diarrhea (3 pts) and nausea (3 pts). Grade 3 cytopenias were seen in all pts and grade 3 nausea in 1 pt. Three pts had neutropenic fever. Treatment during first course was interrupted after 5 days of infusion in 1 pt due to grade 3 congestive heart failure (CHF). This pt received his second course of treatment without recurrence of CHF. In conclusion, HHT has modest activity in intermediate to high risk MDS. After first interim analysis, the study meets criteria for continued accrual.


Leukemia ◽  
2017 ◽  
Vol 32 (2) ◽  
pp. 413-418 ◽  
Author(s):  
V Santini ◽  
B Allione ◽  
G Zini ◽  
D Gioia ◽  
M Lunghi ◽  
...  

2017 ◽  
Vol 35 (24) ◽  
pp. 2745-2753 ◽  
Author(s):  
Mikkael A. Sekeres ◽  
Megan Othus ◽  
Alan F. List ◽  
Olatoyosi Odenike ◽  
Richard M. Stone ◽  
...  

Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m2/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications ( P < .001).With a median follow-up of 23 months (range, 1 to 43 months), the ORR was 38% for patients receiving azacitidine, 49% for azacitidine plus lenalidomide ( P = .14 v azacitidine), and 27% for azacitidine plus vorinostat ( P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications.


2001 ◽  
Vol 120 (5) ◽  
pp. A280-A280
Author(s):  
S HANAUER ◽  
P MINER ◽  
A KESHAVARZIAN ◽  
E MORRIS ◽  
B SALZBERG ◽  
...  

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