Phase II trial with sequential clofarabine and cyclophosphamide for refractory and relapsed philadelphia-negative adult acute lymphoblastic leukemia. Results of the GIMEMA LAL 1610 protocol

Renato Bassan, Monica Fumagalli, Sabina Chiaretti, Ernesta Audisio, Nicola Cascavilla, Stefania Paolini, Mario Delia, Elisa Cerqui, Caterina Micò, Francesco Fabbiano, Martina Canichella, Anna Maria Scattolin, Paola Perfetti, Francesca Paoloni, Mariangela Iodice, Antonella Vitale, Irene Della Starza, Paola Fazi, Marco Vignetti, Robin Foà

Research output: Contribution to journalArticle

Abstract

Clofarabine (CLO) and cyclophosphamide (CY) combinations were tested in late stage refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) with disappointing results and high-grade toxicity. We designed a sequential 5-day combination of CLO 40 mg/m2/d plus CY 400 mg/m2/d as first salvage for Philadelphia-negative ALL patients refractory or relapsed until 24 months from complete remission (CR). Primary endpoint was an overall response rate (ORR) ≥ 40%. Among 26 study patients (median age 40.5 years) ORR was 57.6% (CR with complete [n = 8] or incomplete [n = 7] hematologic recovery). Despite severe myelotoxicity, no dose-limiting toxicity suggested de-intensification of CLO schedule. With a median follow-up of 17.0 months, median and 1-year overall and disease-free survival were 6.5 months and 28.6%, and 3.7 months and 28.1%, respectively. This association was tolerable and more effective in patients younger than 40 years with B-precursor ALL, longer first CR, not previously transplanted and achieving CR with full hematological recovery.

Original languageEnglish
JournalLeukemia and Lymphoma
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • acute lymphoblastic leukemia
  • Chemotherapeutic approaches
  • clofarabine

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Bassan, R., Fumagalli, M., Chiaretti, S., Audisio, E., Cascavilla, N., Paolini, S., Delia, M., Cerqui, E., Micò, C., Fabbiano, F., Canichella, M., Scattolin, A. M., Perfetti, P., Paoloni, F., Iodice, M., Vitale, A., Della Starza, I., Fazi, P., Vignetti, M., & Foà, R. (2019). Phase II trial with sequential clofarabine and cyclophosphamide for refractory and relapsed philadelphia-negative adult acute lymphoblastic leukemia. Results of the GIMEMA LAL 1610 protocol. Leukemia and Lymphoma. https://doi.org/10.1080/10428194.2019.1639170