administration of graspa (suspension of erythrocytes encapsulating l-asparaginase) in elderly patients with first line acute lymphoblastic leukemia

Conditions: Acute Lymphoblastic Leukemia

Summary: the main purpose of this study is to determine the maximum tolerated and efficient dose of graspa® in combination with polychemotherapy treatment of elderly patients with all, 55 years and over, philadelphia chromosome-negative (all ph-).

this open label, non randomised, multicentric and national phase iia study was designed to evaluate the safety and efficacy of graspa®, a suspension of red blood cells encapsulating e. coli l-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the european working group on adult all (ewall) for frontline therapy of patients with all ph-, aged 55 years old and over. patients with a good performance status (who score ≤2) and a newly diagnosed all ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with granulocyte colony stimulating factor (g-csf) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses. graspa® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.

Eligibility criteria:
inclusion criteria: * patient aged ≥55 years old * with newly diagnosed all without prior treatment * capable to receive polychemotherapy (world health organization (who) performance status ≤2) * with or without meningeal disease * having signed an informed consent form * subscribed to social security insurance exclusion criteria: * all translocation(9;22) and/or bcr-abl (breakpoint cluster region-abelson) positive * performance status incompatible with chemotherapy treatment (who score \>2) * patient presenting with a general or visceral contraindication to intensive treatment including : * cardiac insufficiency defined as left ventricular ejection fraction \<50% of the theoretical value * plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges, except if related to all * aspartate aminotransferase (asat) or alanine aminotransferase (alat) levels 5 times greater than the upper limit of laboratory ranges, except if related to all * patient with another evolutive cancer other than all * severe evolutive infection, or human immunodeficiency virus (hiv) seropositive or, active hepatitis related to b or c viral infection * prior treatment with l-asparaginase (irrespective of the form) * history of grade 3 transfusional incident (life threatening) * patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible red blood cells concentrate * patient included in another clinical trial during the last 4 weeks

Keywords: acute lymphoblastic leukemia elderly patient asparaginase