Abstract
The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m(2) per day, cyclophosphamide 440 mg/m(2) per day, and etoposide 100 mg/m(2) per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.
Publication types
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Clinical Trial, Phase II
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine Nucleotides / administration & dosage*
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Adenine Nucleotides / adverse effects
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Adolescent
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents, Alkylating / administration & dosage
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Antineoplastic Agents, Alkylating / adverse effects
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Agents, Phytogenic / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Arabinonucleosides / administration & dosage*
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Arabinonucleosides / adverse effects
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Child
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Child, Preschool
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Clofarabine
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Cyclophosphamide / administration & dosage*
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Cyclophosphamide / adverse effects
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Etoposide / administration & dosage*
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Etoposide / adverse effects
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Female
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Humans
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Infant
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Kaplan-Meier Estimate
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Male
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Nucleoside Transport Proteins / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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RNA, Messenger / metabolism
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Recurrence
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Remission Induction
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Risk Factors
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Young Adult
Substances
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Adenine Nucleotides
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Antineoplastic Agents
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Antineoplastic Agents, Alkylating
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Antineoplastic Agents, Phytogenic
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Arabinonucleosides
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Nucleoside Transport Proteins
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RNA, Messenger
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Etoposide
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Clofarabine
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Cyclophosphamide
Associated data
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ClinicalTrials.gov/NCT00315705