A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents (CAALL-F01)

Assistance Publique - Hôpitaux de Paris

Status and phase: Active, not recruiting; Phase 3

Conditions: Acute Lymphoblastic Leukemia

Treatments: Drug: pegaspargase 1250 IU/m2 x 2; Drug: pegaspargase 2500 IU/m2 x 1

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02716233

P091205

Details and patient eligibility

About

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.

Enrollment: 2,044 patients

Sex: All

Ages: 12 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children and adolescents Age > 12 months but < 18 yearsB-lineage or T- lineage ALL
• Written informed consent obtained before day 8 of treatment

Non inclusion criteria:

• L3 (Burkitt's leukemia) (LMB type protocols)
• Mixed Phenotype Acute Leukemia (WHO criteria).
• Infant ALL (age ≤ 365 days (Interfant 06 protocol)
• Secondary leukemia
• Patients previously treated with chemotherapy (steroid exposed patients can be included and stratified according to Section 3.5) Known allergy to pegylated products
• Pregnancy. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant must have a negative serum pregnancy before inclusion and a reliable contraception except oral contraceptives. The contraception should be maintained throughout the study and for 3 months after treatment discontinuation.
• Known HIV positivity
• CNS thrombosis during Prophase

Exclusion criteria

• Ph+/BCR-ABL ALL (ESPhALL protocol)
• CNS thrombosis before D12

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,044 participants in 2 patient groups

Arm 1

Active Comparator group

Description:

pegaspargase 2500 IU/m2 x 1: infusion of a conventional dose of pegaspargase during induction therapy: 2500 IU/m2x1

Treatment:

Drug: pegaspargase 2500 IU/m2 x 1

Arm 2

Experimental group

Description:

pegaspargase 1250 IU/m2 x 2: fractionation of the 2500 IU/m2 pegaspargase dose in two infusions of 1250 IU/m2 each during delayed intensification

Treatment:

Drug: pegaspargase 1250 IU/m2 x 2