Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02716233
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: pegaspargase 1250 IU/m2 x 2 Drug: pegaspargase 2500 IU/m2 x 1 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1578 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
Study Start Date : April 2016
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : April 2026


Arm Intervention/treatment
Active Comparator: Arm 1
pegaspargase 2500 IU/m2 x 1: infusion of a conventional dose of pegaspargase during induction therapy: 2500 IU/m2x1
Drug: pegaspargase 2500 IU/m2 x 1
only for ALL of standard risk and medium risk
Other Name: ONCASPAR 2500 IU/m2 x 1

Experimental: Arm 2
pegaspargase 1250 IU/m2 x 2: fractionation of the 2500 IU/m2 pegaspargase dose in two infusions of 1250 IU/m2 each
Drug: pegaspargase 1250 IU/m2 x 2
only for ALL of standard risk and medium risk
Other Name: ONCASPAR 1250 IU/m2 x 2




Primary Outcome Measures :
  1. Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy [ Time Frame: Day 33 ]
    asparaginase activity > 100 IU/L

  2. Incidence of directly asparaginase-related severe toxicities (Grade ≥ 3 as assessed by CTCAE v4.0) observed during induction therapy [ Time Frame: Between Day 12 of induction and Day 8 of consolidation ]
    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


Secondary Outcome Measures :
  1. Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L [ Time Frame: Day 33 of induction ]
  2. Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy [ Time Frame: Day 40 of induction ]
  3. Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L [ Time Frame: Day 40 of induction ]
  4. Incidence of antibodies against asparaginase, measured in serum [ Time Frame: Day 4 of delayed intensification ]
  5. Incidence of silent inactivation [ Time Frame: First 6-9 months ]
    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

  6. Percentage of patients without switch to Erwinia asparaginase [ Time Frame: First 6-9 months ]
  7. Percentage of patients receiving more than 95% of the intended dose of asparaginase [ Time Frame: First 6-9 months ]
  8. Morphological Complete Remission (CR) rates [ Time Frame: Day 35-Day 42 ]
    Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).

  9. Minimal Residual Disease (MRD) [ Time Frame: Day 35-Day 42, Day 65-Day 105 ]

    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).


  10. Cumulative Incidence of relapses [ Time Frame: 5 years ]
    Assessed on the whole population or on subgroups (B-Lineage ALL, T-cell ALL).

  11. Cumulative Incidence of relapse according to site of relapse [ Time Frame: 5 years ]

    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).


  12. All other adverse events related to asparaginase [ Time Frame: within the first 7 weeks (Day 49) of treatment and anyway before Day 8 of consolidation ]
    Drug-induced hyperglycemia or diabetes, coagulopathy, allergy Non CNS thrombosis Grade 1-2 Adverse Events (AE): pancreatitis, hyperbilirubinemia

  13. Late adverse events related to asparaginase [ Time Frame: after Day 49 of induction or anyway at Day 8 of consolidation or after ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02716233


Contacts
Layout table for location contacts
Contact: André Baruchel, MD +33 1 40 03 53 88 andre.baruchel@aphp.fr
Contact: Yves Bertrand, MD +33 4 69 16 65 70 yves.bertrand@ihope.fr

Locations
Layout table for location information
France
CHU Recruiting
Amiens, France, 80054
Contact: Catherine Devoldere, MD         
CHU Recruiting
Angers, France, 49033
Contact: Isabelle Pellier, MD         
CHRU Recruiting
Besançon, France, 25030
Contact: Pauline Simon, MD         
CHU Recruiting
Bordeaux, France, 33076
Contact: Yves Perel, MD         
CHU Recruiting
Brest, France, 29609
Contact: Liana Carausu, MD         
CHU Recruiting
Caen, France, 14033
Contact: Odile Minckes, MD         
CHU Recruiting
Clermont-Ferrand, France, 63003
Contact: Justyna Kanold, MD         
CHU Recruiting
Dijon, France, 21079
Contact: Elodie Colomb, MD         
CHU Recruiting
Grenoble, France, 38043
Contact: Dominique Plantaz, MD         
CHU Recruiting
Lille, France, 59037
Contact: Françoise Mazingue, MD         
CHU Recruiting
Limoges, France, 87042
Contact: Caroline Oudot, MD         
Chu-Ihope Recruiting
Lyon, France, 69373
Contact: Yves Bertrand, MD       yves.bertrand@ihope.fr   
CHU Recruiting
Marseille, France, 13385
Contact: Gérard Michel, MD         
CHU Recruiting
Montpellier, France, 34295
Contact: Nicolas Sirvent, MD         
CHU Recruiting
Nancy, France, 54511
Contact: Claudine Schmitt, MD         
CHU Recruiting
Nantes, France, 44093
Contact: Caroline Thomas, MD         
CHU Recruiting
Nice, France, 06200
Contact: Pierre-Simon Rohrlich, MD         
CHU Saint Louis Recruiting
Paris, France, 75010
Contact: Nicolas Boissel, MD         
CHU Armand Trousseau Recruiting
Paris, France, 75012
Contact: Arnaud Petit, MD         
CHU Robert Debré Recruiting
Paris, France, 75019
Contact: André Baruchel, MD       andre.baruchel@aphp.fr   
CHU Recruiting
Poitiers, France, 86000
Contact: Frédéric Millot, MD         
CHU Recruiting
Reims, France, 51100
Contact: Stéphanie Gordes-Grosjean, MD         
CHU Recruiting
Rennes, France, 35203
Contact: Virginie Gandemer, MD         
CHU Recruiting
Rouen, France, 76031
Contact: Pascale Schneider, MD         
CHU Recruiting
Saint Etienne, France, 42270
Contact: Sandrine Thouvenin-Doulet, MD         
CHU Recruiting
Strasbourg, France, 67098
Contact: Patrick Lutz, MD         
CHU Recruiting
Toulouse, France, 31059
Contact: Geneviève Plat, MD         
CHu Recruiting
Tours, France, 37044
Contact: Pascale Blouin, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Shire

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02716233     History of Changes
Other Study ID Numbers: AOM10205
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pegaspargase
Asparaginase
Antineoplastic Agents