GRASPA Treatment for Patients With Acute Myeloblastic Leukemia
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
myeloid, leukemia
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: GRASPA
Type: Drug
Overall Status
Recruiting
Summary
The protocol aims at adding GRASPA (L-asparaginase encapsulated in red blood cells) to standard chemotherapy (low-dose cytarabine) to treat patients older than 65 years diagnosed with AML and unfit for intensive chemotherapy.

The investigators Assume a 75% improvement in median Progression Free survival (PFS) in the L-asparaginase (GRASPA) plus low-dose cytarabine group compared to median PFS in the low-dose cytarabine group (control).
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 current study with Red Blood Cells (RBC) encapsulating ASNase (GRASPA®) 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.

Aim Considering the promising results of ASNase for AML treatment and the better safety profile offered by RBC encapsulating ASNase (GRASPA®), 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.

Progression-free survival (time elapsed between treatment initiation and disease progression/death) will be evaluated as a primary endpoint. A 75% improvement in the median progression-free survival is assumed in the experimental group vs control group. Percentages of remission (complete and partial), survival (event-free and overall), patient quality of life, general safety, pharmacodynamic/pharmacokinetic and immunogenicity of GRASPA® will be also evaluated.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 85 Years
Minimum Age: 65 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patient over 65 years old and less than 85 years old

- Newly diagnosed Acute Myeloid Leukemia or post myelodysplastic syndrome diagnosed in the 6 months prior 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)

Exclusion Criteria:

- Patients with M3 AML of French American British classification ( Acute Promyelocytic Leukemia)

- Patients with AML involving chromosome 16 abnormalities or translocation (8:21)

- History of grade 3-4 pancreatitis or grade 3-4 thromboembolic event

- Presenting with a general or visceral contraindication (Uncontrolled or severe cardiovascular disease ; Plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges ; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels, 3.5 times greater than the upper limit of laboratory ranges ; 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

- Has known or suspected hypersensitivity or intolerance to mannitol

- Patient presenting contra indication to cytarabine treatment

- Participation in an investigational drug study within the 30 days prior to entry
Locations
Hôpital l'Archet 1
Nice, Alpes Maritimes, France
Status: Not yet recruiting
Institut Paoli Calmettes
Marseille, Bouche du Rhone, France
Status: Not yet recruiting
Hôpital JEAN MINJOZ
Besancon, Doubs, France
Status: Not yet recruiting
Hopital Morvan
Brest, Finistere, France
Status: Not yet recruiting
Hôpital Haut-Lévèque
Pessac, Gironde, France
Status: Recruiting
CHRU de Nîmes
Nimes, Guard, France
Status: Recruiting
Hopital de Hautepierre
Strasbourg, Haut Rhin, France
Status: Recruiting
Hopital De Purpan CHU Toulouse
Toulouse, Haute Garonne, France
Status: Not yet recruiting
Hopital Région d'Annecy
Pringy, Haute Savoie, France
Status: Recruiting
Hôpital Saint Eloi
Montpellier, Hérault, France
Status: Recruiting
Hôtel Dieu - CHU de NANTES
Nantes, Loire Atlantique, France
Status: Recruiting
Institut de Cancérologie de la Loire
Saint-priest-en-jarez, Loire, France
Status: Recruiting
Chu D'Angers
Angers, Maine et Loire, France
Status: Recruiting
Hopital de Brabois
Vandoeuvre Les Nancy, Meurthe et Moselle, France
Status: Recruiting
Hôpital Claude-Huriez
Lille, Nord, France
Status: Not yet recruiting
CHU Estaing
Clermont-ferrand, Puy de Dome, France
Status: Recruiting
hopital de Perpignan
Perpignan, Pyrénées Orientales, France
Status: Not yet recruiting
Centre Léon Bérard
Lyon, Rhone Alpes, France
Status: Not yet recruiting
Centre hospitalier Lyon Sud
Pierre Benite, Rhone Alpes, France
Status: Recruiting
Centre Henri Becquerel
Rouen, Seine Maritime, France
Status: Not yet recruiting
Groupe Hospitalier Sud
Amiens, Somme, France
Status: Recruiting
Start Date
February 2013
Completion Date
March 2017
Sponsors
ERYtech Pharma
Source
ERYtech Pharma
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page