This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day.

Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): Phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial) / Willemze, R; Suciu, S; Muus, P; Halkes, Cj; Meloni, G; Meert, L; Karrasch, M; Rapion, J; Vignetti, M; Amadori, S; de Witte, T; Marie, Jp. - In: ANNALS OF HEMATOLOGY. - ISSN 0939-5555. - 93:6(2014), pp. 965-975. [10.1007/s00277-014-2056-6]

Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): Phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)

Meloni G;Vignetti M;Amadori S;
2014

Abstract

This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day.
2014
Acute myeloid leukemia; Clofarabine; Phase I dose finding study; Adenine Nucleotides; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Consolidation Chemotherapy; Cytarabine; Fatigue; Female; Gastrointestinal Diseases; Humans; Hydroxyurea; Hyperbilirubinemia; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Remission Induction; Risk; Treatment Outcome; Hematology
01 Pubblicazione su rivista::01a Articolo in rivista
Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): Phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial) / Willemze, R; Suciu, S; Muus, P; Halkes, Cj; Meloni, G; Meert, L; Karrasch, M; Rapion, J; Vignetti, M; Amadori, S; de Witte, T; Marie, Jp. - In: ANNALS OF HEMATOLOGY. - ISSN 0939-5555. - 93:6(2014), pp. 965-975. [10.1007/s00277-014-2056-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1189539
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