GRASPA Treatment for Patients With Acute Myeloblastic Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      The protocol aims at adding GRASPA (L-asparaginase encapsulated in red blood cells,
      eryaspase) to standard chemotherapy (low-dose cytarabine) to treat patients older than 65
      years diagnosed with AML and unfit for intensive chemotherapy.
    

Detailed description: 
      L-asparaginase (ASNase) holds a key role in chemotherapy for Acute Lymphoblastic Leukemia
      (ALL) in children and young adults. In elderly patients, its efficacy is counterbalanced by
      its toxicity, which impairs its use. However, a study conducted with GRASPA (L-asparaginase
      encapsulated in red blood cells, eryaspase) in elderly ALL (study reference "GRASPALL-GRAAL
      SA2 2008") showed that efficacy/safety profile was positive, paving the way for introducing
      ASNase benefit into chemotherapy for elderly patients.

      In adults, Capizzi (1988) reported a significant benefit of ASNase associated with high-dose
      cytarabine treatment (HiDAC) in Acute Myeloid Leukemia (AML). Indeed, there was an overall
      statistically superior complete remission rate for HiDAC/ASNase (40%) vs HiDAC (24%) and an
      overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks vs 15.9 weeks).

      Another study in elderly patients also displayed positive results for ASNase treatment
      (Petti, 1989), as well as recent single case reports that point out the potential benefit of
      ASNase in different AML or mixed lineage leukemia (Horikoshi, 2009; Rubnitz, 2009).

      Our preclinical results also showed that an AML cell line and blast cells from the bone
      marrow of AML patients were sensitive to ASNase in vitro.

      However, up to now, the toxicity of ASNase for elderly had prevented its use in this
      population that represents the majority of AML patients.

      Considering the promising results of ASNase for AML treatment and the better safety profile
      offered by GRASPA (L-aspariginase encapsulated in red blood cells, erysapase), a multicenter,
      randomized, controlled IIb trial is open for recruitment. Efficacy and tolerability of GRASPA
      plus low-dose cytarabine will be evaluated versus low-dose cytarabine alone in treatment of
      AML patients over 65 year-old, unfit for intensive chemotherapy.

      One hundred and twenty-three patients (65-85 year-old) newly diagnosed for AML are planned
      for inclusion in the study.

      A 2:1 randomization will be respected (82 patients treated with GRASPA® plus low-dose
      cytarabine and 41 patients treated with low-dose cytarabine alone). Each patient will be
      followed for 24 months.
    

Intervention name(s): GRASPA
Intervention type(s): Drug
Intervention description(s): Patients receiving Intervention (experimental group) will be treated with one injection of graspa per cycle of treatment, each cycle during 28 days, for a duration up to 24 cycles maximum
Other intervention name(s): L-asparaginase encapsulated in red blood cells
Intervention MeSH terms: Asparaginase; Eryaspase
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: myeloid; leukemia