Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia

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Abstract

Clofarabine was studied as therapy for patients with relapsed, and refractory acute leukemias in phase 1-2 dose escalation with mitoxantrone and etoposide,. A tolerable dose was identified which resulted in an overall response of 36%, and median overall survival (OS) of 167 days. This combination is active in a patient population without good standard therapy and merits further study. Background: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. Patients and Methods: In the phase I portion of this study clofarabine was given 20 or 25 mg/m2 daily for 5 days (Days 2-6) with etoposide 100 mg/m2 from day 1 to 5 and mitoxantrone 8 mg/m2 from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m2 daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. Results: Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. Conclusion: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalClinical Lymphoma, Myeloma and Leukemia
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2015

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Mitoxantrone
Etoposide
Leukemia
Survival
Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nucleosides
Acute Myeloid Leukemia
clofarabine
Blood Platelets
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

@article{45c60a947bd046b185dcb804db7f7b56,
title = "Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia",
abstract = "Clofarabine was studied as therapy for patients with relapsed, and refractory acute leukemias in phase 1-2 dose escalation with mitoxantrone and etoposide,. A tolerable dose was identified which resulted in an overall response of 36{\%}, and median overall survival (OS) of 167 days. This combination is active in a patient population without good standard therapy and merits further study. Background: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. Patients and Methods: In the phase I portion of this study clofarabine was given 20 or 25 mg/m2 daily for 5 days (Days 2-6) with etoposide 100 mg/m2 from day 1 to 5 and mitoxantrone 8 mg/m2 from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m2 daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. Results: Five of 22 patients (23{\%}) achieved complete response (CR), and 3 (13{\%}) achieved CR with incomplete platelet recovery; an overall response rate of 36{\%}. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. Conclusion: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.",
author = "Abbi, {Kamal K.S.} and Witold Rybka and Ehmann, {W. Christopher} and David Claxton",
year = "2015",
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language = "English (US)",
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T1 - Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia

AU - Abbi, Kamal K.S.

AU - Rybka, Witold

AU - Ehmann, W. Christopher

AU - Claxton, David

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Clofarabine was studied as therapy for patients with relapsed, and refractory acute leukemias in phase 1-2 dose escalation with mitoxantrone and etoposide,. A tolerable dose was identified which resulted in an overall response of 36%, and median overall survival (OS) of 167 days. This combination is active in a patient population without good standard therapy and merits further study. Background: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. Patients and Methods: In the phase I portion of this study clofarabine was given 20 or 25 mg/m2 daily for 5 days (Days 2-6) with etoposide 100 mg/m2 from day 1 to 5 and mitoxantrone 8 mg/m2 from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m2 daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. Results: Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. Conclusion: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.

AB - Clofarabine was studied as therapy for patients with relapsed, and refractory acute leukemias in phase 1-2 dose escalation with mitoxantrone and etoposide,. A tolerable dose was identified which resulted in an overall response of 36%, and median overall survival (OS) of 167 days. This combination is active in a patient population without good standard therapy and merits further study. Background: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. Patients and Methods: In the phase I portion of this study clofarabine was given 20 or 25 mg/m2 daily for 5 days (Days 2-6) with etoposide 100 mg/m2 from day 1 to 5 and mitoxantrone 8 mg/m2 from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m2 daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. Results: Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. Conclusion: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.

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DO - 10.1016/j.clml.2014.06.005

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