Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
21 septembre 2021 mis à jour par: ERYtech Pharma
An Escalating Dose Phase IIa Study of L-Asparaginase Encapsulated in Erythrocytes (GRASPA®) in Association With Polychemotherapy During Induction Phase for Treatment of Elderly Patients With Acute Lymphoblastic Leukaemia (ALL), Aged 55 Years and Over, With Philadelphia Chromosome-negative (ALL Ph-)
The main purpose of this study is to determine the maximum tolerated and efficient dose of GRASPA® in combination with polychemotherapy treatment of elderly patients with ALL, 55 years and over, Philadelphia chromosome-negative (ALL Ph-).
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over.
Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses.
GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
Type d'étude
Interventionnel
Inscription (Réel)
30
Phase
- Phase 2
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
55 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Patient aged ≥55 years old
- With newly diagnosed ALL without prior treatment
- Capable to receive polychemotherapy (World Health Organization (WHO) performance status ≤2)
- With or without meningeal disease
- Having signed an Informed Consent Form
- Subscribed to social security insurance
Exclusion Criteria:
- ALL translocation(9;22) and/or BCR-ABL (Breakpoint Cluster Region-Abelson) positive
- Performance status incompatible with chemotherapy treatment (WHO score >2)
Patient presenting with a general or visceral contraindication to intensive treatment including :
- 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 ALL
- Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) levels 5 times greater than the upper limit of laboratory ranges, except if related to ALL
- Patient with another evolutive cancer other than ALL
- Severe evolutive infection, or Human Immunodeficiency Virus (HIV) seropositive or, active hepatitis related to B or C viral infection
- Prior treatment with L-asparaginase (irrespective of the form)
- History of grade 3 transfusional incident (life threatening)
- Patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible Red Blood Cells Concentrate
- Patient included in another clinical trial during the last 4 weeks
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: GRASPA 50 IU/kg
Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase.
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
Expérimental: GRASPA 100 IU/kg
Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
Expérimental: GRASPA 150 IU/kg
Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Délai: 7 days after the first administration of GRASPA® during Induction 1
|
The main evaluation criterion is a composite efficacy/toxicity criterion.
Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA®
|
7 days after the first administration of GRASPA® during Induction 1
|
|
Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
Délai: Induction 1 and Induction 2
|
Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities.
|
Induction 1 and Induction 2
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Plasma Concentrations of Asparagine
Délai: Induction 1 & Induction 2
|
Mean plasma concentration of asparagine over time.
Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L.
|
Induction 1 & Induction 2
|
|
Plasma Concentrations of Aspartic Acid
Délai: Induction 1 and Induction 2
|
Mean plasma concentration of aspartic acid over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamine
Délai: Induction 1 and Induction 2
|
Mean glutamine concentration over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamic Acid.
Délai: Induction 1 and Induction 2
|
Mean glutamic acid concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Asparagine
Délai: Induction 1 and Induction 2
|
Mean cerebral spinal fluid asparagine concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Aspartic Acid
Délai: Induction 1 and Induction 2
|
Mean cerebral spinal fluid aspartic acid concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamine
Délai: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamine concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamic Acid
Délai: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamic acid concentration
|
Induction 1 and Induction 2
|
|
Summary of Free Asparaginase Over Time
Délai: Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Summary of Encapsulated Asparaginase (U/L) Over Time
Délai: Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Number of Patients Positive for Anti-L-asparaginase Antibodies
Délai: Induction 1 and Induction 2
|
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
|
Induction 1 and Induction 2
|
|
Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
Délai: 1 and 2 months
|
CR was defined using:
|
1 and 2 months
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Mathilde Hunault-Berger, Professor, University Hospital, Angers
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 avril 2009
Achèvement primaire (Réel)
1 janvier 2011
Achèvement de l'étude (Réel)
1 octobre 2012
Dates d'inscription aux études
Première soumission
16 janvier 2012
Première soumission répondant aux critères de contrôle qualité
30 janvier 2012
Première publication (Estimation)
1 février 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
15 octobre 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
21 septembre 2021
Dernière vérification
1 juin 2018
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- GRASPALL/GRAALLSA2-2008
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Non
Description du régime IPD
Not applicable for this study
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