EsPhALL

With the coming into effect of the amendment from 31.12.2009 (end of the randomization) Good-risk and Poor Risk Ph+ALL patients will receive IMATINIB starting on day 15 during Induction phase and continuously troughout the consolidation and reinduction phase of chemotherapy.
The use of IMATINIB is recommended in all HSCT recipients. Imatinib administration is suggested throughout the first year posttransplantation, till day +365 from HSCT.

Primary objective:
To evaluate in patients with Ph+ALL the efficacy and safety of IMATINIB continuous exposure on top of intensive, BFM-type
chemotherapy. The endpoint for response will be the evaluation on the long-term clinical outcome Secondary objectives A. To determine the safety and feasibility.

Secondary objectives:
A. To compare the outcome with historical controls of patients treated with BFM oriented protocols (including patients treated
with Imatinib in the original EsPhALL protocol) and with recent results from the COGAALL0031 (Children Oncology Group-
USA) study, which adopts a more intensive chemotherapy approach than BFM.
B. To evaluate in patients with Ph+ALL the efficacy and safety of IMATINIB continuous exposure on top of intensive, BFM-type
chemotherapy. The endpoint for response will be the evaluation on the long-term clinical outcome.

All patients will receive the induction phase according to the national/group study treatment protocols. In Germany this are in the moment the trials AIEOP-BFM 2009 or CoALL-08-09 for patients >1 year, or Interfant 06 for patients < 1 year at diagnosis. As soon, as a positive BCR/ABL result is kwown (Cytogenetics, FISH or PCR) and the patient is eligable for the EsPhALL-trial, the participation in this trial should be announced to the AIEOP-BFM or CoALL trial.
With the closure of the ranomization Imatinib 300 mg/m2 daily will be introduced starting on day 15 of Induction phase and will go on continuously troughout the consolidation and reinduction phase of chemotherapy.

All patients will be screened for an HLA-identical family or unrelated donor.
Good-risk patients: patients with a genotype-matched donor (9/10 or 10/10), will receive HSCT,
while the others will continue on chemotherapy, thus receiving IMATINIB in combination with the
standard chemotherapy.

Poor-Risk patients: patients will be eligible for any type of donor (matched or mismatched family
donors, unrelated or haploidentical donors). Patients not transplanted will continue on chemotherapy, thus receiving IMATINIB in combination with the standard chemotherapy.

• Children and adolescents aged 1-17 years at diagnosis, with documented by either cytogenetics, PCR or FISH for bcr-abl
• Eligible for the current local prospective therapeutic study of childhood ALL
• Informed consent was given by the parents or by legal guardian.

• Abnormal hepatic function (ALAT/ASAT >10 times the upper limit of the normal range)
• Abnormal renal function (creatinine >1.5 times the upper limit of the normal range or a calculated creatinine clearance of 80 ml/
• min or less, adjusted to a body surface area of 1.73 m2)
 
• Active systemic bacterial, fungal or viral infection as documented by positive cultures, radiological imaging techniques, septic shock symptoms.