High-Dose Imatinib for Relapsed/Refractory c-Kit Positive Acute Myelogenous Leukemia (AML)

A Phase II Trial Evaluating the Safety and the Efficacy of High-Dose Imatinib in Relapsed/Refractory c-Kit Positive and BCR-Abl Negative AML Patients

This is a multicenter open-label phase II trial of high dose imatinib mesylate in patients with AML in first or second relapse, or with refractory disease. Daily dosing of imatinib 600 mg/day is planned for one month or until progression of disease. Dose increase to 800 mg/ day imatinib is permitted for 2 additional months in the event of response failure. Response is assessed after 1, 2 and 3 months of treatment by bone marrow aspirate.

Daily dosing of imatinib 600 mg/day is planned for one month or until progression of disease. Dose increase to 800 mg/ day imatinib is permitted for 2 additional months in the event of response failure. Novartis provided supplies of imatinib for all patients included in the study.

Inclusion Criteria:

• age > 18 years,

• AML in first or second relapse,

• refractory AML

• performance status of 0-2 on the Eastern Cooperative Oncology Group scale,

• adequate hepatic and renal functions (AST or ALT <= 5 times the upper limit of normal

• creatinine < 2 times the upper limit of normal)

  • 20% blasts in bone marrow,
  • 70% of bone marrow blast population c-kit positive as assessed by immunophenotyping

• Bcr-Abl negative chromosomal analysis (assessed by fluorescence in situ hybridization; FISH), and no chromosome 5-12 translocation

Exclusion Criteria:

• Previous treatment by Imatinib
• Secondary AML