TY - JOUR
T1 - Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia
AU - Kantarjian, Hagop
AU - Gandhi, Varsha
AU - Cortes, Jorge
AU - Verstovsek, Srdan
AU - Du, Min
AU - Garcia-Manero, Guillermo
AU - Giles, Francis
AU - Faderl, Stefan
AU - O'Brien, Susan
AU - Jeha, Sima
AU - Davis, Jan
AU - Shaked, Zeev
AU - Craig, Adam
AU - Keating, Michael
AU - Plunkett, William
AU - Freireich, Emil J.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - In a phase 2 study, 62 patients with relapsed and refractory acute myeloid leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days, every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had a partial response (PR), and 9 (15%) achieved CR but without platelet recovery (CRp), for an overall response rate of 48%. In AML, responses were noted in 2 (18%) of 11 patients in first salvage with short first CR (≤ 12 months), in 7 (87%) of 8 patients with longer first CR, and in 8 (67%) of 12 patients in second or subsequent salvage. Responses were observed in 4 of 8 patients with high-risk MDS (50%), in 7 (64%) of 11 with CML-BP, and in 2 (17%) of 12 with ALL. Severe reversible liver dysfunction was noted in 15% to 25%. After the first clofarabine infusion, responders accumulated more clofarabine triphosphate in blasts compared with nonresponders (median 18 vs 10 μM; P = .03). This increased only in responders (median, 1.8-fold; P = .008) after the second clofarabine infusion. In summary, clofarabine is active in acute leukemias and MDS; cellular pharmacokinetics may have prognostic significance.
AB - In a phase 2 study, 62 patients with relapsed and refractory acute myeloid leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days, every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had a partial response (PR), and 9 (15%) achieved CR but without platelet recovery (CRp), for an overall response rate of 48%. In AML, responses were noted in 2 (18%) of 11 patients in first salvage with short first CR (≤ 12 months), in 7 (87%) of 8 patients with longer first CR, and in 8 (67%) of 12 patients in second or subsequent salvage. Responses were observed in 4 of 8 patients with high-risk MDS (50%), in 7 (64%) of 11 with CML-BP, and in 2 (17%) of 12 with ALL. Severe reversible liver dysfunction was noted in 15% to 25%. After the first clofarabine infusion, responders accumulated more clofarabine triphosphate in blasts compared with nonresponders (median 18 vs 10 μM; P = .03). This increased only in responders (median, 1.8-fold; P = .008) after the second clofarabine infusion. In summary, clofarabine is active in acute leukemias and MDS; cellular pharmacokinetics may have prognostic significance.
UR - http://www.scopus.com/inward/record.url?scp=0141482004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141482004&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-03-0925
DO - 10.1182/blood-2003-03-0925
M3 - Article
C2 - 12791647
AN - SCOPUS:0141482004
SN - 0006-4971
VL - 102
SP - 2379
EP - 2386
JO - Blood
JF - Blood
IS - 7
ER -