Acute Myeloid Leukaemia MedDRA version: 14.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: GRASPA
Product Code: PF001
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: L-asparaginase encapsulated in erythrocytes
Current Sponsor code: L-asparaginase encapsulate
Sponsors
ERYTECH Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient over 65 years old and less than 85 years old - Newly diagnosed Acute Myeloid Leukemia (AML) or post myelodysplastic syndrome diagnosed in the 6 months prior to study enrollment - Unfit for intensive chemotherapy (at risk to suffer treatment related pejorative toxicities /early death) or patient unwilling to receive intensive chemotherapy - WHO performance status =2 and estimated life expectancy = 3 months - Eligible to receive low-dose cytarabine treatment - Evidence of post-menopausal status for female (absence of menstruation for 12 months) - Subscription to social security insurance - Provision of written Informed Consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 123
Exclusion criteria
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) - History of grade 3-4 pancreatitis or grade 3-4 thromboembolic event (according NCI-CTCAE Version 4.0) - Presenting with a general or visceral contraindication including : * 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. 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 AML * AST or ALT levels, 3.5 times greater than the upper limit of laboratory ranges, except if related to AML * Patient presenting evolutive cancer other than AML, except in situ basal-cell carcinoma or in situ cervix cancer * Severe evolutive infection, or, HIV seropositive or, active hepatitis related to B or C viral infection - History of Grade 3 Transfusional incident (life threatening) - Has known or suspected hypersensitivity or intolerance to mannitol, or heparin - Patient presenting contra indication to cytarabine treatment (hypersensitivity to cytarabine, antimitotic treatment, preexisting medullary aplasia, toxic degenerative encephalopathy - especially after methotrexate treatment or ioniding radiations-, yellow fever vaccination) - Participation in an investigational drug study within the 30 days prior to entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate Progression Free Survival (PFS) in AML patients older than 65 unfit for intensive chemotherapy, when treated with GRASPA (L-asparaginase encapsulated in erythrocytes) plus low-dose cytarabine compared to low-dose cytarabine alone.;Secondary Objective: To evaluate - Response to treatment - Event Free Survival - Overall survival - Patient transfusion needs - Patients Quality of life evolution - Number of hospitalization - Global safety of GRASPA in combination with cytarabine - Pharmacokinetic and pharmacodynamic parameters of GRASPA - Immunogenicity of GRASPA Exploratory: Asparagine Synthetase exploration (in bone marrow cells);Primary end point(s): Progression free survival (PFS) defined as the time elapsed between treatment initiation and disease progression or death related to disease (AML or study treatment);Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of Primary end points are described in E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of patients with Complete remission (CR), Complete remission with incomplete recovery (neutrophile or platelet regeneration, CRi), Partial remission (PR) - Event Free Survival defined as the time elapsed between treatment initiation and treatment failure, or treatment stop/delayed from toxicity reason, or disease progression, or death from any cause - Overall survival defined as the time elapsed between treatment initiation and death from any cause - Percentage of patients who need transfusions (red cells and/or platelets), number of transfusion by patient - Patient quality of life (patient survey) - Number of hospitalization (except scheduled protocol visit) - General safety of GRASPA® in combination with low-dose cytarabine, specific attention to : * Grade 3 to 4 of Pancreatic toxicity * Grade 3 or 4 of hepatic toxicity, allergic reaction or thromboembolic event * All other non hematologic grade 4 toxicities (NB grading reference used : NCI CTCAE version 4.0) - Pharmacodynamic and pharmacokinetic parameters of GRASPA: * Plasmatic concentrations of asparagine, aspartate, glutamine, glutamate * Total L-asparaginase activity * Immunogenicity : titer of anti-L-asparaginase antibodies Exploratory endpoints : - Asparagine synthetase, Asparagine synthetase mRNA expression and in vitro sensitivity to asparaginase on the tumoral bone marrow cells harvested before treatment;Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of Secondary end points are described in E.5.2 | — |
Countries
Finland, Germany, Spain
Contacts
Public ContactJerome Bailly
ERYTECH Pharma
Outcome results
None listed