Clinical trial NCT02716233: A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
Official title: A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2016-03-23
Enrollment: 1578
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A still major question in the field of acute lymphoblastic leukemia (ALL) in children - an extremely heterogeneous disease though curable in 80-90% of children and 70-80% of the adolescents - is the optimal use of L-asparaginase (ASNase). It is known that administering ASNase results in the depletion of asparagine circulating in the blood, which starves the leukemic cells and results in their death. But indeed the use of ASNase varies between protocols considering the different brands, the dose and the administration modalities. Oncaspar (PEGylated E. coli asparaginase, pegaspargase) was thus developed with the goal of reducing the immunogenicity of the native ASNase.

This is a French prospective multicentric cohort study of children and adolescents with ALL, stratified on (i) the type of ALL ( B vs T) and (ii) the anticipated risk (stratified in 3 groups for childhood B-cell precursor (BCP)-ALL and 2 groups for T-cell ALL).

It aims to answer to two different issues:

1. Randomized question: what is the best way to administer pegaspargase? A cohort of children and adolescents with standard or medium risk ALL will be randomized to receive during induction either one infusion of ONCASPAR® 2500 IU/m2 at D12 or two infusions of ONCASPAR® at 1250 IU/m2 each at D12 and D26. Patients will then receive 2500 IU/m2 or 1250 IU/m2 per dose during consolidation and delayed intensification according to the initial arm of randomization.
2. Non randomized question: In the High/Very High Risk groups, a non randomized intensification of the scheme of asparaginase administration is proposed during induction therapy: 2 infusions of 2500 IU/m2/day (D12 and D26) will be administered. All patients will receive 2500 IU/m2 per dose during consolidation and delayed intensifications.


Eligibility criteria: Inclusion Criteria:

* ALL L1 or L2
* B-lineage or T- lineage ALL

Exclusion Criteria:

* L3 (Burkitt's leukemia)
* Mixed Phenotype Acute Leukemia (WHO criteria).
* Infant ALL (age ≤ 365 days)
* Philadelphia (Ph)+/Breakpoint Cluster region (BCR)-Abelson (ABL) ALL

Primary outcomes:
measure: Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy
timeFrame: Day 33
measure: Incidence of directly asparaginase-related severe toxicities (Grade ≥ 3 as assessed by CTCAE v4.0) observed during induction therapy
timeFrame: Between Day 12 of induction and Day 8 of consolidation
Secondary outcomes:
measure: Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L
timeFrame: Day 33 of induction
measure: Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy
timeFrame: Day 40 of induction
measure: Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L
timeFrame: Day 40 of induction
measure: Incidence of antibodies against asparaginase, measured in serum
timeFrame: Day 4 of delayed intensification
measure: Incidence of silent inactivation
timeFrame: First 6-9 months
measure: Percentage of patients without switch to Erwinia asparaginase
timeFrame: First 6-9 months
measure: Percentage of patients receiving more than 95% of the intended dose of asparaginase
timeFrame: First 6-9 months
measure: Morphological Complete Remission (CR) rates
timeFrame: Day 35-Day 42
measure: Minimal Residual Disease (MRD)
timeFrame: Day 35-Day 42, Day 65-Day 105
measure: Cumulative Incidence of relapses
timeFrame: 5 years
measure: Cumulative Incidence of relapse according to site of relapse
timeFrame: 5 years
measure: All other adverse events related to asparaginase
timeFrame: within the first 7 weeks (Day 49) of treatment and anyway before Day 8 of consolidation
measure: Late adverse events related to asparaginase
timeFrame: after Day 49 of induction or anyway at Day 8 of consolidation or after
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU
city: Angers
country: France
facility: CHU
city: Besançon
country: France
facility: CHRU
city: Bordeaux
country: France
facility: CHU
city: Brest
country: France
facility: CHU
city: Caen
country: France
facility: CHU
city: Clermont-Ferrand
country: France
facility: CHU
city: Dijon
country: France
facility: CHU
city: Grenoble
country: France
facility: CHU
city: Lille
country: France
facility: CHU
city: Limoges
country: France
facility: CHU
city: Lyon
country: France
facility: Chu-Ihope
city: Marseille
country: France
facility: CHU
city: Montpellier
country: France
facility: CHU
city: Nancy
country: France
facility: CHU
city: Nantes
country: France
facility: CHU
city: Nice
country: France
facility: CHU
city: Paris
country: France
facility: CHU Saint Louis
city: Paris
country: France
facility: CHU Armand Trousseau
city: Paris
country: France
facility: CHU Robert Debré
city: Poitiers
country: France
facility: CHU
city: Reims
country: France
facility: CHU
city: Rennes
country: France
facility: CHU
city: Rouen
country: France
facility: CHU
city: Saint Etienne
country: France
facility: CHU
city: Strasbourg
country: France
facility: CHU
city: Toulouse
country: France
facility: CHU
city: Tours
country: France
facility: CHu
Study officials:
References: