search
Back to results

Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children (ESPHALL)

Primary Purpose

Acute Lymphoblastic Leukemia, Philadelphia Chromosome

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Standard chemotherapy + Imatinib
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Chemotherapy, Leukemia, Children, Philadelphia chromosome, Protein-tyrosine kinase inhibitor

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Service d'hématologie pédiatrique CHRU
  • Service hématologie pédiatrique Hôpital Saint-Jacques
  • Service d'hémato-oncologie - Hôpital des Enfants Pellegrin
  • Hôpital Morvan
  • Hématologie oncologie pédiatrique-CHU Caen
  • Hémato-Oncologie et Thérapie Cellulaire Pédiatrique - Hôtel Dieu
  • Hémato-Oncologie Pédiatrique - Hôpital d'Enfants
  • Pédiatrie CHU - Hôpital Nord
  • Hôpital Jeanne de Flandre
  • Limoges University Hospital
  • Hôpital DEBROUSSE Institut d'hématologie et d'oncologie pédiatrique
  • Hôpital Arnaud de Villeneuve
  • Hématologie Pédiatrique - Hôpital Trousseau
  • Hémato-immunologie-Robert Debré
  • Hématologie Hôpital Jean Bernard
  • Hématologie pédiatrique-Hopital américain
  • Service d'hématologie pédiatrique - Hôpital Sud
  • Service d'Immuno Hémato Oncologie Pédiatrique - Hôpital Charles Nicolle
  • Hématologie, Oncologie pédiatrique-CHU Saint Etienne
  • Hopital des enfants
  • CHU- Centre Gatien de Clocheville
  • Hôpital d'enfants

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Good risk Ph+ALL

Poor risk Ph+ALL

Arm Description

For protocols which adopt a steroid prephase: patients who are Prednisone-good responder and achieve CR after the induction course. For protocols which do not adopt steroid prephase: patients who have M1/M2 BM at day 15 or M1 BM at day 21 and achieve CR after the induction course. Expected stratification in this group: 70-75%.

For protocols which adopt a steroid prephase: patients who are Prednisone poor-responders. For protocol which do not adopt a steroid prephase: patients who have M3 BM at day 15 or M2/M3 BM at day 21. For all protocols: patients who do not achieve CR after the induction course. Expected stratification: 25-30%.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Compare long term outcome between patients treated by BFM-chemotherapy and patient undergoing more intensive chemotherapy (protocole COGAALL0031 : Children Oncology Group-USA).
Long-term clinical outcome : Disease free survival (DFS), Event-Free Survival (EFS) and Overall Survival (OS) in each risk groups.
Pattern of molecular response (MRD)
Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group.

Full Information

First Posted
February 3, 2006
Last Updated
May 22, 2023
Sponsor
Rennes University Hospital
Collaborators
Ministry of Health, France, Novartis
search

1. Study Identification

Unique Protocol Identification Number
NCT00287105
Brief Title
Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children
Acronym
ESPHALL
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
December 2005 (Actual)
Primary Completion Date
March 30, 2016 (Actual)
Study Completion Date
March 3, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital
Collaborators
Ministry of Health, France, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Philadelphia Chromosome
Keywords
Chemotherapy, Leukemia, Children, Philadelphia chromosome, Protein-tyrosine kinase inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Good risk Ph+ALL
Arm Type
Other
Arm Description
For protocols which adopt a steroid prephase: patients who are Prednisone-good responder and achieve CR after the induction course. For protocols which do not adopt steroid prephase: patients who have M1/M2 BM at day 15 or M1 BM at day 21 and achieve CR after the induction course. Expected stratification in this group: 70-75%.
Arm Title
Poor risk Ph+ALL
Arm Type
Other
Arm Description
For protocols which adopt a steroid prephase: patients who are Prednisone poor-responders. For protocol which do not adopt a steroid prephase: patients who have M3 BM at day 15 or M2/M3 BM at day 21. For all protocols: patients who do not achieve CR after the induction course. Expected stratification: 25-30%.
Intervention Type
Drug
Intervention Name(s)
Standard chemotherapy + Imatinib
Other Intervention Name(s)
Glivec, Gleevec
Intervention Description
Patients receive Imatinib together with the standard chemotherapy regimen of phase IB and after each of three consecutive blocks of the standard chemotherapy in the consolidation phase
Primary Outcome Measure Information:
Title
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Compare long term outcome between patients treated by BFM-chemotherapy and patient undergoing more intensive chemotherapy (protocole COGAALL0031 : Children Oncology Group-USA).
Time Frame
2 years
Title
Long-term clinical outcome : Disease free survival (DFS), Event-Free Survival (EFS) and Overall Survival (OS) in each risk groups.
Time Frame
2 years
Title
Pattern of molecular response (MRD)
Time Frame
5 time points between S4 and S22
Title
Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Biondi, MD
Organizational Affiliation
Ospedale S. Gerardo - Monza
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Virginie Gandemer, MD
Organizational Affiliation
Rennes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service d'hématologie pédiatrique CHRU
City
Amiens
ZIP/Postal Code
80080
Country
France
Facility Name
Service hématologie pédiatrique Hôpital Saint-Jacques
City
Besancon
ZIP/Postal Code
25000
Country
France
Facility Name
Service d'hémato-oncologie - Hôpital des Enfants Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Hôpital Morvan
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
Hématologie oncologie pédiatrique-CHU Caen
City
Caen
Country
France
Facility Name
Hémato-Oncologie et Thérapie Cellulaire Pédiatrique - Hôtel Dieu
City
Clermont-Ferrand
ZIP/Postal Code
63058
Country
France
Facility Name
Hémato-Oncologie Pédiatrique - Hôpital d'Enfants
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Pédiatrie CHU - Hôpital Nord
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hôpital Jeanne de Flandre
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Limoges University Hospital
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hôpital DEBROUSSE Institut d'hématologie et d'oncologie pédiatrique
City
Lyon
Country
France
Facility Name
Hôpital Arnaud de Villeneuve
City
Montpellier
Country
France
Facility Name
Hématologie Pédiatrique - Hôpital Trousseau
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Hémato-immunologie-Robert Debré
City
Paris
Country
France
Facility Name
Hématologie Hôpital Jean Bernard
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Hématologie pédiatrique-Hopital américain
City
Reims
Country
France
Facility Name
Service d'hématologie pédiatrique - Hôpital Sud
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Service d'Immuno Hémato Oncologie Pédiatrique - Hôpital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Hématologie, Oncologie pédiatrique-CHU Saint Etienne
City
Saint Etienne
Country
France
Facility Name
Hopital des enfants
City
Toulouse
Country
France
Facility Name
CHU- Centre Gatien de Clocheville
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Hôpital d'enfants
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
22898679
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.
Results Reference
result
PubMed Identifier
30501871
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.
Results Reference
result
PubMed Identifier
33242441
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.
Results Reference
derived
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/30501871/
Description
Primary Publication

Learn more about this trial

Safety and Efficacy of Imatinib Added to Chemotherapy in Treatment of Ph+ Acute Lymphoblastic Leukemia in Children

We'll reach out to this number within 24 hrs