Clinical trial NCT01518517: GRASPA (Erythrocytes Encapsulating L-asparaginase) in Patients With Relapse of Acute Lymphoblastic Leukemia
Official title: Phase 2/3 Study Evaluating Efficacy and Safety of Erythrocytes Encapsulating L-asparaginase (GRASPA)Versus Reference L-asparaginase Treatment in Combination With Standard Polychemotherapy in Patient With First Recurrence of Philadelphia Negative Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Lymphoblastic Leukemia, in Relapse
Keywords: acute lymphoblastic leukemia
relapse
asparaginase
Lead sponsor: ERYtech Pharma
Sponsor class: INDUSTRY
First posted: 2012-01-26
Enrollment: 85
Sex: ALL
Minimum age (years): 1
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA improves pharmacokinetics, tolerability and maintain circulating asparaginase activity due to the protective barrier of the erythrocyte membrane.

This study is run to confirm the benefit/risk profile of GRASPA at 150 IU/kg in combination with the COOPRALL regimen in adults and children patients with relapsed ALL, with or without known hypersensitivity to L-asparaginase.

Detailed description: This open, randomized international Phase 2/3 study will enrol patients with relapsed ALL. The co-primary endpoints were the duration of asparagine depletion \< 2µmol/L and the incidence of asparaginase hypersensitivity during induction. Key secondary endpoints are complete remission (CR), minimal residual disease (MRD), event free survival (EFS) and overall survival (OS).The study was powered to detect 3-fold difference in the incidence of allergic reactions between treatments. patients will be randomized to GRASPA or to Reference L-asparaginase. Patients with history of hypersensitivity to previous L-asparaginase treatment will be treated with GRASPA (exploratory arm)

Eligibility criteria: Inclusion Criteria:

* Patient from 1 to 55 years old (Children and adolescents from 1 to 17 years/ Adults from 18 to 55 years)
* Patients with 1st ALL relapse, which could be either isolated bone marrow relapse, or combined (medullary and extra-medullary) relapse, or extra-medullary isolated relapse; or lymphoblastic lymphoma (excepted Burkitt lymphoma) OR Failure to ALL first line treatment (no complete remission obtained)
* Patient previously treated with free E.Coli L-asparaginase form or pegylated one
* Performance Status ≤ 2 (WHO score)
* Patient informed and consent provided (the 2 parents need to consent when children are below 18)

Exclusion Criteria:

* ALL t(9;22) and/or BCR-ABL positive (Philadelphia chromosome positive)
* Patient with 2nd relapse and over
* Women of childbearing potential without effective contraception as well as pregnant or breast feeding women
* Patient unable to receive treatments used in global chemotherapy protocols, due to general or visceral conditions such as:Severe cardiac impairment (NYHA grade 3 or 4 cardiomyopathy)/Serum creatinine 2 x ULN unless related to ALL /ALT or AST 5 x ULN unless related to ALL /Pancreatitis history /Other malignancy that ALL / Severe Infection, HIV positive, active hepatitis related to B or C virus infection / Trisomy 21 / Other serious conditions according to investigator's opinion
* Known grade 4 allergic reaction to E.Coli L-asparaginase (according NCI-CTCAE, Version 3.0)
* History of grade 3 transfusional incident
* Presence of specific anti-erythrocyte antibodies preventing from getting a compatible erythrocyte concentrate for the patient
* Patient under concomitant treatment likely to cause hemolysis
* Patient undergoing yellow fever vaccination
* Patient under phenytoin treatment
* Patient included in previous clinical study less than 6 weeks ago

Primary outcomes:
measure: Duration of Asparaginase Activity >100 U/L During Induction
timeFrame: Induction treatment period (i.e. 28 days)
measure: Allergic Reaction During Induction Phase
timeFrame: Induction treatment period (i.e. 28 days)
Secondary outcomes:
measure: Complete Remission (CR)
timeFrame: Induction treatment period (i.e. 28 days)
measure: Overall Survival (OS)
timeFrame: Overall trial period to 36 months
measure: Event Free Survival
timeFrame: Overall trial period to 36 months
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Hopital Des Enfants Reine Fabiola
city: Liege
country: Belgium
facility: Chr de La Citadelle
city: Angers
country: France
facility: Chu D'Angers
city: Besancon
country: France
facility: Hopital Saint Jacques
city: Bordeaux
country: France
facility: Hopital Pellegrin Enfants
city: Clermont Ferrand
country: France
facility: Chu Estaing
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Grenoble
country: France
facility: Chu Grenoble
city: Lille
country: France
facility: Chru Lille - Hop Jeanne de Flandres
city: Lyon
country: France
facility: Institut Hematologie Oncologie Pediatrique
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Hopital Mere Enfant
city: Nantes
country: France
facility: Hotel Dieu
city: Nice
country: France
facility: Hopital de L'Archet 2
city: Paris
country: France
facility: Hopital Armand Trousseau
city: Paris
country: France
facility: Hopital Robert Debre
city: Paris
country: France
facility: Hopital Saint Louis
city: Pessac
country: France
facility: Hopital Haut-Leveque
city: Pierre Benite
country: France
facility: Hopital Lyon Sud
city: Rennes
country: France
facility: Chru Hopital Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Etienne
country: France
facility: Chu Hopital Nord
city: Saint Priest En Jarez
country: France
facility: Institut Cancerologie de La Loire
city: Strasbourg
country: France
facility: Hopital de Hautepierre
city: Toulouse
country: France
facility: Chu de Toulouse Enfants
city: Valenciennes
country: France
facility: Hotel Dieu
city: Vandoeuvre Les Nancy
country: France
facility: Hopital Brabois Enfants
city: Vandoeuvre Les Nancy
country: France
facility: Hopital de Brabois
Study officials:
name: Yves Bertand, MD
role: PRINCIPAL_INVESTIGATOR
References: