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)
Brigitte Nelken MD
Pediatric Hematology, CHRU Lille, Lille, France
Search for more papers by this authorHelene Cave PhD
Department of Genetics, Robert-Debré Hospital, Paris, France
Search for more papers by this authorGuy Leverger MD
Pediatric Haematology and Oncology Unit, Hopital Trousseau, Paris, France
Search for more papers by this authorClaire Galambrun MD
Pediatric Hematology Department, Hopital de La Timone, Marseille, France
Search for more papers by this authorGenevieve Plat MD
Department of Pediatric Onco-Hematology, CHU-Hopital Purpan, Toulouse, France
Search for more papers by this authorClaudine Schmitt MD
Pediatric Hematology Oncology, CHU de Nancy, Vandoeuvre, France
Search for more papers by this authorCaroline Thomas MD
Hematology Department, CHU de Nantes, France
Search for more papers by this authorCécile Vérité MD
Pediatric Oncology Unit, University Hospital, Bordeaux, France
Search for more papers by this authorBenoit Brethon MD
Pediatric Hematology, Hopital Robert Debre AP-HP, Paris, France
Search for more papers by this authorVirginie Gandemer MD
Department of Pediatric Hematology/Oncology, CHU-Hopital Sud, Rennes, France
Search for more papers by this authorYves Bertrand MD
Institute of Pediatric Hematology and Oncology, University Hospital, Lyon, France
Search for more papers by this authorAndré Baruchel MD
Department of Pediatric Hematology, Robert Debré Hospital, Paris, France
Search for more papers by this authorCorresponding Author
Pierre Rohrlich MD
Pediatric Hematology Unit, CHU Jean Minjoz Hospital, Besançon, France
Correspondence to: Pierre S. Rohrlich, Hemato-Oncologie Pédiatrique, Hôpital ARCHET 1, BP 3079, 06202 NICE CEDEX 3, France. E-mail: [email protected]
Search for more papers by this authorBrigitte Nelken MD
Pediatric Hematology, CHRU Lille, Lille, France
Search for more papers by this authorHelene Cave PhD
Department of Genetics, Robert-Debré Hospital, Paris, France
Search for more papers by this authorGuy Leverger MD
Pediatric Haematology and Oncology Unit, Hopital Trousseau, Paris, France
Search for more papers by this authorClaire Galambrun MD
Pediatric Hematology Department, Hopital de La Timone, Marseille, France
Search for more papers by this authorGenevieve Plat MD
Department of Pediatric Onco-Hematology, CHU-Hopital Purpan, Toulouse, France
Search for more papers by this authorClaudine Schmitt MD
Pediatric Hematology Oncology, CHU de Nancy, Vandoeuvre, France
Search for more papers by this authorCaroline Thomas MD
Hematology Department, CHU de Nantes, France
Search for more papers by this authorCécile Vérité MD
Pediatric Oncology Unit, University Hospital, Bordeaux, France
Search for more papers by this authorBenoit Brethon MD
Pediatric Hematology, Hopital Robert Debre AP-HP, Paris, France
Search for more papers by this authorVirginie Gandemer MD
Department of Pediatric Hematology/Oncology, CHU-Hopital Sud, Rennes, France
Search for more papers by this authorYves Bertrand MD
Institute of Pediatric Hematology and Oncology, University Hospital, Lyon, France
Search for more papers by this authorAndré Baruchel MD
Department of Pediatric Hematology, Robert Debré Hospital, Paris, France
Search for more papers by this authorCorresponding Author
Pierre Rohrlich MD
Pediatric Hematology Unit, CHU Jean Minjoz Hospital, Besançon, France
Correspondence to: Pierre S. Rohrlich, Hemato-Oncologie Pédiatrique, Hôpital ARCHET 1, BP 3079, 06202 NICE CEDEX 3, France. E-mail: [email protected]
Search for more papers by this authorAbstract
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/m2/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/m2), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m2), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m2. 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/m2/d in this combination which appeared feasible and effective in this population. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
Supporting Information
Additional supporting information may be found in the online version of this article at the publisher's web-site.
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