Study of Imatinib-Combined Chemotherapy for BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL)

Phase 2 Study of Imatinib-Combined Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia

The purpose of this study is to determine the clinical efficacy and safety of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Philadelphia chromosome (Ph) is a translocation abnormality leading to the formation of the BCR-ABL gene rearrangement. This genetic abnormality occurs in up to 30% of adult acute lymphoblastic leukemia (ALL), and its presence is known to be the most adverse prognostic factor for ALL. Because long-term survival cannot be achieved by conventional chemotherapy alone, there is a clear medical need for alternative treatment approaches. Imatinib is a potent selective inhibitor of the BCR-ABL protein kinase, and it has been reported that single-agent imatinib induced response in a substantial proportion of Ph-positive ALL (Ph+ALL) patients, but that the response was not durable. The Japan Adult Leukemia Study Group (JALSG) has therefore started a phase 2 study designed to evaluate the clinical effect of imatinib-combined chemotherapy on newly diagnosed BCR-ABL-positive ALL.

Inclusion Criteria:

• Previously untreated BCR-ABL-positive ALL
• Age between 15 and 64 years
• Performance status between 0 and 3 (ECOG criteria)
• Adequate functioning of the liver (serum bilirubin level < 2.0 mg/dL), kidneys (serum creatinine level < 2.0 mg/dL), and heart (left ventricular ejection fraction greater than 50% and no severe abnormalities detected on electrocardiograms and echocardiographs)
• Written informed consent to participate in the trial

Exclusion Criteria:

• Uncontrolled active infection
• Another severe and/or life-threatening disease
• Positive for HIV antibody and/or hepatitis B surface (HBs) antigen tests
• Another primary malignancy which is clinically active and/or requires medical interventions
• Pregnant and/or lactating women
• Past history of renal failure