Liposomal Anthracyclin in the Treatment of Elderly ALL

A Multicentric Phase II-III Randomized Study Safety of Intraveinous Liposomal Pegylated Doxorubicin Versus Continuous Infusion of Doxorubicin During Induction Treatment of Acute Lymphoblastic Leukemia in Patients

Phase II multicentric study comparing VAD regimen with continuous infusion over 96 hours of doxorubicin, vincristine and dexamethasone to a 90 minutes infusion of equivalent doses of Dox li-PEG, bolus infusion of vincristine and dexamethasone

Patients aged 55 years or over will be assessed for response to steroids from day -7 to day 0 During steroid therapy, Ph status will be determinated : patients with Ph+ ve ALL will be treated according to the another French Protocol while patients with Ph-ve ALL will be included in the "caelyx" protocol and randomly allocated to induction with VAD or with vadox-li-Peg (caelyx). A second course of induction therapy with VAD+ cyclophosphamide of Vadox-li-peg+ cyclophosphamide(according to the initial randomization arm) will then be given to all patients. Consolidation therapy included 2 courses of vad or of vadox-li-Peg , according to the initial random allocation, followed by two courses of cytarabine,cyclophosphamide and thioguanine. During induction and consolidation therapy, doxorubicin and liposomal pegylated doxorubicin pharmacokinetics will be assessed in all patients. Treatment of occult CNS invasion includes skull radiotherapy and 6 intrathecal injections(steroÏds+methotrexate) A two years maintenance course with 6 mercaptopurine and methotrexate will then be offered to all patients.

Number of patients alive by day 113 ( last injection of anthracycline ) and having received a full course of induction/consolidation therapy

Inclusion Criteria: 55 years of age and older ECOG performance </=2 or >/=3 VIH negative Absence of previous ALL treatment Informed consent signed SGPT and Bilirubin < 4x upper limit of normal Normal creatinine for age cardiac state compatible with anthacyclin Exclusion Criteria: ALL with Philadelphia Chromosome ALL3 CML blasts crisis Cardiac insufficiency and/ or left ventricular ejection fraction < 50% Evolutive infection Presence of other evolutifs cancer or ongoing treatment mental status incompatible with inform consent

Hunault-Berger M, Leguay T, Thomas X, Legrand O, Huguet F, Bonmati C, Escoffre-Barbe M, Legros L, Turlure P, Chevallier P, Larosa F, Garban F, Reman O, Rousselot P, Dhedin N, Delannoy A, Lafage-Pochitaloff M, Bene MC, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study. Haematologica. 2011 Feb;96(2):245-52. doi: 10.3324/haematol.2010.027862. Epub 2010 Oct 22.