Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia

Hagop Kantarjian, Varsha Gandhi, Jorge Cortes, Srdan Verstovsek, Min Du, Guillermo Garcia-Manero, Francis Giles, Stefan Faderl, Susan O'Brien, Sima Jeha, Jan Davis, Zeev Shaked, Adam Craig, Michael Keating, William Plunkett, Emil J. Freireich

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2379-2386
Number of pages8
JournalBlood
Volume102
Issue number7
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Refractory materials
Leukemia
Salvaging
Emitter coupled logic circuits
Pharmacokinetics
Platelets
Liver
Myelodysplastic Syndromes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
clofarabine
Clinical Studies
Liver Diseases
Blood Platelets
Recovery

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kantarjian, H., Gandhi, V., Cortes, J., Verstovsek, S., Du, M., Garcia-Manero, G., ... Freireich, E. J. (2003). Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood, 102(7), 2379-2386. https://doi.org/10.1182/blood-2003-03-0925

Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. / Kantarjian, Hagop; Gandhi, Varsha; Cortes, Jorge; Verstovsek, Srdan; Du, Min; Garcia-Manero, Guillermo; Giles, Francis; Faderl, Stefan; O'Brien, Susan; Jeha, Sima; Davis, Jan; Shaked, Zeev; Craig, Adam; Keating, Michael; Plunkett, William; Freireich, Emil J.

In: Blood, Vol. 102, No. 7, 01.10.2003, p. 2379-2386.

Research output: Contribution to journalArticle

Kantarjian, H, Gandhi, V, Cortes, J, Verstovsek, S, Du, M, Garcia-Manero, G, Giles, F, Faderl, S, O'Brien, S, Jeha, S, Davis, J, Shaked, Z, Craig, A, Keating, M, Plunkett, W & Freireich, EJ 2003, 'Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia', Blood, vol. 102, no. 7, pp. 2379-2386. https://doi.org/10.1182/blood-2003-03-0925
Kantarjian, Hagop ; Gandhi, Varsha ; Cortes, Jorge ; Verstovsek, Srdan ; Du, Min ; Garcia-Manero, Guillermo ; Giles, Francis ; Faderl, Stefan ; O'Brien, Susan ; Jeha, Sima ; Davis, Jan ; Shaked, Zeev ; Craig, Adam ; Keating, Michael ; Plunkett, William ; Freireich, Emil J. / Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. In: Blood. 2003 ; Vol. 102, No. 7. pp. 2379-2386.
@article{dfca6984657f4abdb08887dfd3cadc3b,
title = "Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia",
abstract = "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.",
author = "Hagop Kantarjian and Varsha Gandhi and Jorge Cortes and Srdan Verstovsek and Min Du and Guillermo Garcia-Manero and Francis Giles and Stefan Faderl and Susan O'Brien and Sima Jeha and Jan Davis and Zeev Shaked and Adam Craig and Michael Keating and William Plunkett and Freireich, {Emil J.}",
year = "2003",
month = "10",
day = "1",
doi = "10.1182/blood-2003-03-0925",
language = "English (US)",
volume = "102",
pages = "2379--2386",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

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

VL - 102

SP - 2379

EP - 2386

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -