TY - JOUR
T1 - Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia
AU - Hijiya, Nobuko
AU - Thomson, Blythe
AU - Isakoff, Michael S.
AU - Silverman, Lewis B.
AU - Steinherz, Peter G.
AU - Borowitz, Michael J.
AU - Kadota, Richard
AU - Cooper, Todd
AU - Shen, Violet
AU - Dahl, Gary
AU - Thottassery, Jaideep V.
AU - Jeha, Sima
AU - Maloney, Kelly
AU - Paul, Jo Anne
AU - Barry, Elly
AU - Carroll, William L.
AU - Gaynon, Paul S.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of venoocclusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.
AB - The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of venoocclusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.
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U2 - 10.1182/blood-2011-08-374710
DO - 10.1182/blood-2011-08-374710
M3 - Article
C2 - 21967976
AN - SCOPUS:82955207681
SN - 0006-4971
VL - 118
SP - 6043
EP - 6049
JO - Blood
JF - Blood
IS - 23
ER -