GRASPA Treatment for Patients With Acute Myeloblastic Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: GRASPA
Intervention description: 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
Intervention MeSH terms: Asparaginase; Eryaspase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 65 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: myeloid; leukemia

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.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patient > 65 years old and < 85 years old

          -  Newly diagnosed Acute Myeloid Leukemia (AML) or post myelodysplastic syndrome
             diagnosed within 6 months prior to study enrollment

          -  Unfit for intensive chemotherapy (at risk to suffer treatment related pejorative
             toxicities /early death) due to the presence of one or more of the following criteria:
             Dependence in activities of daily living owing to the presence of comorbidities other
             than those resulting from the deterioration caused by the neoplastic disease. Presence
             in the patient's medical history of three or more of the following comorbidities, even
             if they are under control with proper treatment: Congestive heart failure, other
             chronic cardiovascular diseases, chronic obstructive pulmonary disease,
             cerebrovascular disease, peripheral neuropathy, chronic kidney failure, hypertension,
             diabetes mellitus, systemic vasculitis, severe arthritis

          -  Presence of geriatric syndromes such as fecal or urinary incontinence, spontaneous
             bone fractures, mild and moderate dementia, or patients who fall repeatedly, or,
             patient unwilling to receive intensive chemotherapy

          -  Eligible to receive low-dose cytarabine treatment

          -  ECOG performance status ≤ 2

          -  Female patients of childbearing potential and males must agree to use adequate
             contraception (e.g., hormonal or barrier method of birth control; abstinence) for the
             duration of study treatment and for 6 months after the last dose of Cytarabine or 3
             months after last dose of GRASPA (whichever is the longest).

          -  Negative serum pregnancy test at study entry for female subjects of childbearing
             potential

          -  Subscription to social security insurance (if applicable, in accordance with local
             regulations)

          -  Ability to understand, and willingness to sign, a written informed consent document
             and to comply with scheduled visits, treatment plans, laboratory tests, and other
             study procedures

        Exclusion criteria:

          -  Patients with M3 AML of FAB classification (APL, acute promyelocytic leukemia)

          -  Patients with AML involving chromosome 16 abnormalities or translocation (8:21)
             (CBF-AML)

          -  Patient with secondary AML subsequent to prior malignant blood disorder such as:
             Myelodysplastic syndrome diagnosed more than 6 months before study entry or
             Myeloproliferative syndrome

          -  Prior therapy to AML (standard therapy or investigational agents)

          -  Inadequate organ function : Uncontrolled or severe cardiovascular disease including
             myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA)
             Class III or IV heart failure, uncontrolled angina, clinically significant pericardial
             disease, or cardiac amyloidosis, Serum creatinine concentration > 2 x ULN (Upper Limit
             of Normal), AST or ALT levels > 3.5xULN or 5xULN if related to AML, Total bilirubin >
             2 x ULN, INR > 1.5, unless patient under chronic treatment with anticoagulants (in
             this case, INR should be within expected ranges for the specific condition),
             Insulin-dependent or uncontrolled diabetes mellitus

          -  Concurrent malignancies other than AML requiring chemotherapy

          -  Severe active infection, HIV seropositivity, or known active type B or C viral
             hepatitis

          -  Known or suspected hypersensitivity or intolerance to mannitol

          -  Breastfeeding or lactating women