A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents

Acute Lymphoblastic Leukemia Clinical Trial

— CAALL-F01  

Official title:

A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02716233
• Other study ID #: AOM10205
• Status: Recruiting
• Phase: Phase 3
• Start date: April 2016
• Est. completion date: April 2026

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: André Baruchel, MD
• Phone: +33 1 40 03 53 88
• Email: andre.baruchel[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1578
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• pegaspargase 1250 IU/m2 x 2
only for ALL of standard risk and medium risk
• pegaspargase 2500 IU/m2 x 1
only for ALL of standard risk and medium risk

Locations

Country	Name	City	State
France	CHU	Amiens
France	CHU	Angers
France	CHRU	Besançon
France	CHU	Bordeaux
France	CHU	Brest
France	CHU	Caen
France	CHU	Clermont-Ferrand
France	CHU	Dijon
France	CHU	Grenoble
France	CHU	Lille
France	CHU	Limoges
France	Chu-Ihope	Lyon
France	CHU	Marseille
France	CHU	Montpellier
France	CHU	Nancy
France	CHU	Nantes
France	CHU	Nice
France	CHU Armand Trousseau	Paris
France	CHU Robert Debré	Paris
France	CHU Saint Louis	Paris
France	CHU	Poitiers
France	CHU	Reims
France	CHU	Rennes
France	CHU	Rouen
France	CHU	Saint Etienne
France	CHU	Strasbourg
France	CHU	Toulouse
France	CHu	Tours

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Shire

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy	asparaginase activity > 100 IU/L	Day 33
Primary	Incidence of directly asparaginase-related severe toxicities (Grade = 3 as assessed by CTCAE v4.0) observed during induction therapy	Incidence of severe toxicities (Grade = 3) directly asparaginase-related (CNS thrombosis, pancreatitis, anaphylaxis, and hyperbilirubinemia) between Day 12 and Day 49 of treatment and anyway before Day 8 of consolidation	Between Day 12 of induction and Day 8 of consolidation
Secondary	Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L		Day 33 of induction
Secondary	Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy		Day 40 of induction
Secondary	Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L		Day 40 of induction
Secondary	Incidence of antibodies against asparaginase, measured in serum		Day 4 of delayed intensification
Secondary	Incidence of silent inactivation	Silent inactivation or subclinical hypersensitivity is defined as a plasma PEGasparaginase activity level <100 IU/L at day 7+/- 1 or <20 IU/L at day 14 +/- 11 after administration in a patient without clinical symptoms of allergy	First 6-9 months
Secondary	Percentage of patients without switch to Erwinia asparaginase		First 6-9 months
Secondary	Percentage of patients receiving more than 95% of the intended dose of asparaginase		First 6-9 months
Secondary	Morphological Complete Remission (CR) rates	Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).	Day 35-Day 42
Secondary	Minimal Residual Disease (MRD)	MRD will be assessed by Ig/T cell receptor (TCR)-based real-time quantitative (RQ)-polymerase chain reaction (PCR), assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).; Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).	Day 35-Day 42, Day 65-Day 105
Secondary	Cumulative Incidence of relapses	Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).	5 years
Secondary	Cumulative Incidence of relapse according to site of relapse	Bone-Marrow (BM) relapses, central nervous system (CNS) relapses, gonadal relapses, combined relapses.; Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).	5 years
Secondary	All other adverse events related to asparaginase	Drug-induced hyperglycemia or diabetes, coagulopathy, allergy Non CNS thrombosis Grade 1-2 Adverse Events (AE): pancreatitis, hyperbilirubinemia	within the first 7 weeks (Day 49) of treatment and anyway before Day 8 of consolidation
Secondary	Late adverse events related to asparaginase		after Day 49 of induction or anyway at Day 8 of consolidation or after