Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML1208)

• Maximum-tolerated dose of everolimus [ Time Frame: At one year from study entry ] [ Designated as safety issue: Yes ]
  MTD of RAD given in combination with the MICE regimen
  
  

• Safety [ Time Frame: At one year from study entry ] [ Designated as safety issue: Yes ]
  
• Complete remission rate [ Time Frame: At one year from study entry ] [ Designated as safety issue: No ]
  Complete remission rate (CR + CRi) following one or two induction courses.
  
  

Drug: cytarabine
Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.
Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Drug: etoposide
Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.
Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Drug: everolimus

Remission induction therapy: test dose once a day by mouth, on days 1-21 (21 days).

Consolidation therapy: dose as defined by the cohort once a day by mouth, on days 1-10.

Other Name: RAD001
Drug: idarubicin
Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.
Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Drug: mitoxantrone hydrochloride
Remission induction therapy: by short i.v. infusion on days 1, 3 and 5

OBJECTIVES:

Primary

• To determine the maximum-tolerated dose of everolimus in combination with standard remission-induction therapy comprising mitoxantrone hydrochloride, cytarabine, and etoposide (MICE-regimen) followed by consolidation therapy comprising idarubicin, cytarabine, and etoposide in older patients with newly diagnosed acute myeloid leukemia.

Secondary

• To determine the safety profile of this regimen in these patients.
• To determine the anti-leukemic activity (complete remission rate [complete remission and complete remission with incomplete blood count recovery]) following one or two induction courses.

OUTLINE: This is a multicenter, dose-escalation study of everolimus.

• Standard remission-induction therapy: Patients receive mitoxantrone hydrochloride IV over 30 minutes on days 1, 3, and 5; cytarabine IV continuously on days 1-7; etoposide IV over 1 hour on days 1-3; and oral everolimus once a day on days 1-21. Patients with partial remission (PR) receive a second induction course, beginning 7-17 days after completion of induction course 1. Patients with complete remission or complete remission with incomplete blood count recovery (CR/CRi) after induction therapy proceed to consolidation therapy; patients who have failed to achieve PR after induction course 1 or a CR/CRi after induction course 2 are removed from study.
• Consolidation therapy: Beginning within 3 weeks from CR/CRi documentation, patients receive idarubicin IV over 30 minutes on days 1, 3, and 5; cytarabine IV continuously on days 1-5; etoposide IV over 1 hour on days 1-3; and oral everolimus once a day on days 1-10. Patients may receive another course of the consolidation therapy, beginning at least 4 weeks after initiation of consolidation therapy course 1.

After completion of study treatment, patients are followed up once a month for 1 year, every 3 months for 1 year, and then periodically thereafter.