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A Phase I Study of Clofarabine With Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee)
Author(s) -
Nelken Brigitte,
Cave Helene,
Leverger Guy,
Galambrun Claire,
Plat Genevieve,
Schmitt Claudine,
Thomas Caroline,
Vérité Cécile,
Brethon Benoit,
Gandemer Virginie,
Bertrand Yves,
Baruchel André,
Rohrlich Pierre
Publication year - 2016
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25751
Subject(s) - clofarabine , medicine , mitoxantrone , etoposide , gastroenterology , cytarabine , regimen , population , acute leukemia , oncology , chemotherapy , surgery , leukemia , environmental health
Background Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi‐drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. Patients and methods A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m 2 /d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post‐transplant ALL relapse. Results Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose‐limiting toxicity (DLT) appeared at dose level 3 (32 mg/m 2 ), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m 2 ), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m 2 . There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. Conclusion Clofarabine MTD was 32 mg/m 2 /d in this combination which appeared feasible and effective in this population. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.