GRASPA Treatment for Patients With Acute Myeloblastic Leukemia
- Registration Number
- NCT01810705
- Lead Sponsor
- ERYtech Pharma
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 123
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GRASPA GRASPA patients will receive one injection of GRASPA (100 IU/kg) after each course of low-dose cytarabine (see Arm "Control")
- Primary Outcome Measures
Name Time Method Overall Survival Each patient will be followed for a duration of 24 months. OS is defined as the time elapsed between randomization and death from any cause.
- Secondary Outcome Measures
Name Time Method Response to Treatment Each patient will be followed for a duration of 24 months. Percentage of patients with Complete remission (CR), Complete remission with incomplete recovery (neutrophil or platelet regeneration, CRi), Partial remission (PR)
Asparagine Synthetase (Optional) Until patient stops treatment (expected average of 8 months) Asparagine synthetase and in vitro sensitivity to aspariginase on the harvested bone marrow cells
Patient Quality of Life Each patient will be followed for a duration of 24 months. Collecting survey about patients quality of life
Relapse Free Survival Each patient will be followed for a duration of 24 months. Defined only for patients who achieve CR or CRi as the time elapsed between date of CR/CRi and date of disease relapse or death from any cause
Percentage of Patients Who Need Transfusions Until patient stops treatment (expected average of 8 months) Number of transfusions per patient (red blood cells and or platelets)
Number of Hospitalizations Each patient will be followed for a duration of 24 months. Hospitalizations (except schedule protocol visit during the study)
Progression Free Survival (PFS) Each patient will be followed for a duration of 24 months. Defined as the time elapsed between randomization and resistant disease or relapse or death from any cause
Safety of GRASPA Adverse Events and Serious Adverse Events Each patient will be followed for a duration of 24 months. Number of incidences, type, severity and causality of adverse events / serious adverse events
Pharmacodynamic and Pharmacokinetic Parameters of GRASPA Until patient stops treatment (expected average of 8 months) Plasma concentrations of asparagine, aspartate, glutamine, glutamate, whole blood L- asparaginase activity
Immunogenicity Until patient stops treatment (expected average of 8 months) Titer of anti L-asparaginase antibodies
Biomarker Cytogenetic Testing (Optional) Until patient stops treatment (expected average of 8 months) Defined as cytogenetic biomarker testing
Trial Locations
- Locations (21)
Hôpital Claude-Huriez
🇫🇷Lille, Nord, France
CHU Estaing
🇫🇷Clermont-ferrand, Puy De Dome, France
Institut Paoli Calmettes
🇫🇷Marseille, Bouche Du Rhone, France
Hôpital JEAN MINJOZ
🇫🇷Besancon, Doubs, France
Hôpital l'Archet 1
🇫🇷Nice, Alpes Maritimes, France
Hopital Morvan
🇫🇷Brest, Finistere, France
Hopital de Hautepierre
🇫🇷Strasbourg, Haut Rhin, France
Hôpital Haut-Lévèque
🇫🇷Pessac, Gironde, France
CHRU de Nîmes
🇫🇷Nimes, Guard, France
Hopital De Purpan CHU Toulouse
🇫🇷Toulouse, Haute Garonne, France
Hopital Région d'Annecy
🇫🇷Pringy, Haute Savoie, France
Hôpital Saint Eloi
🇫🇷Montpellier, Hérault, France
Institut de Cancérologie de la Loire
🇫🇷Saint-priest-en-jarez, Loire, France
Hôtel Dieu - CHU de NANTES
🇫🇷Nantes, Loire Atlantique, France
Chu D'Angers
🇫🇷Angers, Maine Et Loire, France
Hopital de Brabois
🇫🇷Vandoeuvre Les Nancy, Meurthe Et Moselle, France
hopital de Perpignan
🇫🇷Perpignan, Pyrénées Orientales, France
Centre Léon Bérard
🇫🇷Lyon, Rhone Alpes, France
Centre hospitalier Lyon Sud
🇫🇷Pierre Benite, Rhone Alpes, France
Centre Henri Becquerel
🇫🇷Rouen, Seine Maritime, France
Groupe Hospitalier Sud
🇫🇷Amiens, Somme, France