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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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)

Conditions
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Acute Lymphoblastic Leukemia, Philadelphia Chromosome

Intervention / Treatment
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* Drug: Standard chemotherapy + Imatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Good risk Ph+ALL<br>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%. | Drug: Standard chemotherapy + Imatinib<br>* 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<br>* Other names: Gleevec;|
| Other: Poor risk Ph+ALL<br>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%. | Drug: Standard chemotherapy + Imatinib<br>* 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<br>* Other names: Gleevec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare long term outcome between patients treated by BFM-chemotherapy and patient undergoing more intensive chemotherapy (protocole COGAALL0031 : Children Oncology Group-USA). |  | 2 years | 
| Long-term clinical outcome : Disease free survival (DFS), Event-Free Survival (EFS) and Overall Survival (OS) in each risk groups. |  | 2 years | 
| Pattern of molecular response (MRD) |  | 5 time points between S4 and S22 | 
| Conversion rate to CR in patients resistant to the first part of the induction phase of chemotherapy included in the Poor-risk group. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy, Leukemia, Children, Philadelphia chromosome, Protein-tyrosine kinase inhibitor