Clinical trial NCT00287105: Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children
Official title: An Open-label, Phase II Study to Explore the Safety and Efficacy of Imatinib With Chemotherapy in Pediatric Patients With Ph+ / BCR-ABL+ Acute Lymphoblastic Leukemia (Ph+ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Philadelphia Chromosome
Keywords: Chemotherapy
Leukemia
Children
Philadelphia chromosome
Protein-tyrosine kinase inhibitor
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Novartis
First posted: 2006-02-06
Enrollment: 49
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Imatinib is safe and effective in association with intensive treatment of Ph+ALL in children.

Detailed description: Recent advances in treatment have increased the cure of childhood ALL to 75% or better. However, attempts to improve results for resistant subtypes of ALL, such as Ph+ ALL, have been largely unsuccessful. Imatinib, an inhibitor of protein-tyrosine kinases, is currently being tested in several phase I, II and III trials covering most Chronic Myeloid Leukemia patient populations and patients with overtly relapsed or refractory Ph+ALL. Pediatric patients with Ph+ALL will receive Imatinib, added to intensive, post-induction BFM-type chemotherapy. The endpoint will be the evaluation on the long-term clinical outcome, in particular on the Disease Free Survival (DFS).

Eligibility criteria: Inclusion Criteria:

* Children and adolescents aged 1 to 17 years at diagnostic
* Documented Ph+ ALL
* Eligibility for the current local prospective therapeutic study of childhood ALL
* Informed consent given by the parents or by legal guardian

Exclusion Criteria:

* Abnormal hepatic functions
* Abnormal renal functions
* Active systemic bacterial, fungal or viral infection

Primary outcomes:
measure: Disease free survival (DFS). DFS will be calculated as the time from inclusion to either one of the following events: relapse, death in CCR, second malignancies.
timeFrame: 2 years
Secondary outcomes:
measure: Compare long term outcome between patients treated by BFM-chemotherapy and patient undergoing more intensive chemotherapy (protocole COGAALL0031 : Children Oncology Group-USA).
timeFrame: 2 years
measure: Long-term clinical outcome : Disease free survival (DFS), Event-Free Survival (EFS) and Overall Survival (OS) in each risk groups.
timeFrame: 2 years
measure: Pattern of molecular response (MRD)
timeFrame: 5 time points between S4 and S22
measure: Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group.
timeFrame: 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service d'hématologie pédiatrique CHRU
city: Besancon
country: France
facility: Service hématologie pédiatrique Hôpital Saint-Jacques
city: Bordeaux
country: France
facility: Service d'hémato-oncologie - Hôpital des Enfants Pellegrin
city: Brest
country: France
facility: Hôpital Morvan
city: Caen
country: France
facility: Hématologie oncologie pédiatrique-CHU Caen
city: Clermont-Ferrand
country: France
facility: Hémato-Oncologie et Thérapie Cellulaire Pédiatrique - Hôtel Dieu
city: Dijon
country: France
facility: Hémato-Oncologie Pédiatrique - Hôpital d'Enfants
city: Grenoble
country: France
facility: Pédiatrie CHU - Hôpital Nord
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Limoges
country: France
facility: Limoges University Hospital
city: Lyon
country: France
facility: Hôpital DEBROUSSE Institut d'hématologie et d'oncologie pédiatrique
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Paris
country: France
facility: Hématologie Pédiatrique - Hôpital Trousseau
city: Paris
country: France
facility: Hémato-immunologie-Robert Debré
city: Poitiers
country: France
facility: Hématologie Hôpital Jean Bernard
city: Reims
country: France
facility: Hématologie pédiatrique-Hopital américain
city: Rennes
country: France
facility: Service d'hématologie pédiatrique - Hôpital Sud
city: Rouen
country: France
facility: Service d'Immuno Hémato Oncologie Pédiatrique - Hôpital Charles Nicolle
city: Saint Etienne
country: France
facility: Hématologie, Oncologie pédiatrique-CHU Saint Etienne
city: Toulouse
country: France
facility: Hopital des enfants
city: Tours
country: France
facility: CHU- Centre Gatien de Clocheville
city: Vandoeuvre Les Nancy
country: France
facility: Hôpital d'enfants
Study officials:
affiliation: Ospedale S. Gerardo - Monza
name: Andrea Biondi, MD
role: STUDY_DIRECTOR
affiliation: Rennes University Hospital
name: Virginie Gandemer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Arico M, Rottgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. doi: 10.1016/S1470-2045(12)70377-7. Epub 2012 Aug 14.
citation: Biondi A, Gandemer V, De Lorenzo P, Cario G, Campbell M, Castor A, Pieters R, Baruchel A, Vora A, Leoni V, Stary J, Escherich G, Li CK, Cazzaniga G, Cave H, Bradtke J, Conter V, Saha V, Schrappe M, Grazia Valsecchi M. Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial. Lancet Haematol. 2018 Dec;5(12):e641-e652. doi: 10.1016/S2352-3026(18)30173-X.
citation: Tasian SK, Peters C. Targeted therapy or transplantation for paediatric ABL-class Ph-like acute lymphocytic leukaemia? Lancet Haematol. 2020 Dec;7(12):e858-e859. doi: 10.1016/S2352-3026(20)30369-0. No abstract available.