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).
Pediatr Blood Cancer
; 63(2): 270-5, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26376115
ABSTRACT
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arabinonucleosídeos
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Nucleotídeos de Adenina
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Protocolos de Quimioterapia Combinada Antineoplásica
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Recidiva Local de Neoplasia
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article