Glivec Phase II Pediatric Study

• - Progression-free Survival
• - Overall Survival
• - Safety and tolerability
• - Phrmacokinetic profile and pharmacodynamics of Glivec
• - Pharmacogenetics

The purpose of this study is to determine whether Glivec is effective, in children, adolescents and young adults, in the treatment of malignant disease in which evidence suggests a potential pathogenic role of one or more of the tyrosine kinases known to be inhibited by Glivec.

• Drug: Glivec
• Drug: Gleevec

Inclusion Criteria:

• Patients from 6 months to 21 years of age.
• Malignant disease documented by conventional criteria to be refractory to standard, approved therapy, or for which no conventional therapies of definitive benefit exist.
• Immunohistochemistry documentation of positivity of either Kit (CD117) or PDGF-R in tumor tissue relevant. Each positive tumor will be centrally reviewed before inclusion of the patient in the trial.
• Measurable or evaluable disease.
• WHO Performance status 0,1, or 2 or Lansky Play Scale >= 50%.
• Adequate organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL (or < 5 x ULN if hepatic disease involvement is present), creatinine < 1.5 x ULN, ANC > 1x 109/L, platelets > 75 x 109/L.
• Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing.
• Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
• Life expectancy of more than 6 weeks.
• Written, voluntary, informed consent, including consent for retrieval and investigational use of tissue samples for evaluation signed by parents or young adult patients.
• National and, when needed, local ethical approval.

Exclusion Criteria:

• Patient with hematological disease positive for the chimeric BCR-ABL fusion protein or for c-kit.
• Patient has received any other investigational agents within 28 days of first day of study drug dosing.
• Female patients who are pregnant or breast-feeding.
• Patient has another severe and/or life-threatening medical diseasePatient has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis).
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient has received chemotherapy within 4 weeks (6 weeks for nitrosourea, mitomycin-C or any antibody therapy) prior to study entry unless urgent enrollment needed and approved by the study coordinator.