A PHASE I-II MULTICENTER STUDY OF THE CLORETAZINE-DAUNORUBICIN-ARACYTINE COMBINATION FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA (AML) WITH UNFAVORABLE CYTOGENETICS
- To determine the dose of laromustine that can be combined with daunorubicin
hydrochloride and cytarabine in patients with previously untreated acute myeloid
leukemia with unfavorable cytogenetics. (Phase I)
- To determine the complete remission rate of this regimen as induction therapy. (Phase
- To determine the complete response rate.
- To determine the safety profile of this regimen.
- To determine the overall and relapse-free survival.
- To evaluate the prognostic value of the molecular markers FLT3, duplications of MLL,
OUTLINE: This is a multicenter, phase I dose-escalation study of laromustine followed by a
phase II study.
- Induction treatment: Patients receive laromustine IV on day 4, daunorubicin
hydrochloride IV on days 1-3, and cytarabine IV continuously on days 1-7. Patients not
attaining complete remission (CR) after first induction receive a second induction
treatment comprising daunorubicin hydrochloride IV on days 1-3 and cytarabine IV twice
daily on days 1-4. Patients in CR after 1 or 2 induction treatments proceed to
- Consolidation treatment: Patients receive mini-consolidation treatment comprising
amsacrine on day 1 and cytarabine IV twice daily on days 1-5 followed by 2 courses of
continuing consolidation treatment comprising mitoxantrone hydrochloride on days 1 and
2 and cytarabine IV over 12 hours on days 1-5.
- Allogeneic or autologous stem cell transplantation: Patients receive busulfan four
times daily for 4 days and melphalan followed by allogeneic or autologous stem cell
After completion of study treatment, patients are followed periodically for 5 years.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (phase I)
Norbert Vey, MD
United States: Federal Government