A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia
- Imatinib 200-400 mg p.o. daily x 10 days, Days 1-10 (see dose escalation scheme in
Section 5.4 below).
- Mitoxantrone 10 mg/m2 daily x 5 days, Days 4-8.
- Etoposide 100 mg/m2 daily x 5 days, Days 4-8.
- Cytarabine 1.5 grams/m2 q12h x 4 doses, Days 9-10 (for patients aged 60 years and over,
Only one induction course will be permitted. Only patients achieving CR will proceed to
consolidation and maintenance.
Consolidation therapy, maximum 2 cycles (for patients achieving CR):
- Imatinib 200-400 mg p.o. daily x 8 days, Days 1-8 (see dose escalation scheme in
Section 5.4 below).
- Mitoxantrone 12 mg/m2 daily x 2 days, Days 4-5.
- Cytarabine 3 grams/m2 q12h x 6 doses, Days 4,6,8. For patients aged 60 years and over,
the dose will be reduced to 1.5 grams/m2.
Maintenance therapy (for patients still in CR at end of consolidation):
Imatinib 600 mg p.o. daily, until relapse or toxicity (see dose modification criteria in
Section 5.6.6 below). Patients must receive at least one consolidation cycle before being
permitted to proceed to maintenance therapy (see Section 5.6 for details). Maintenance
therapy with imatinib will be provided for a maximum period of 1 year.
Dose escalation scheme:
Imatinib will be used during induction and consolidation at one of the following dose
Level -1 100 mg daily Level 1 200 mg daily Level 2 300 mg daily Level 3 400 mg daily
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c
Hematologic toxicity Number of days to ANC > 0.5 and 1.0. Number of days until platelets > 20 and > 50, independent of platelet transfusions. Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria Hematologic dose-limiting toxicity (DLT) defined as > 40 days to ANC > 0.5 or platelets > 20 independent of transfusions.
Canada: Ethics Review Committee