A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
- 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
- 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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of everolimus
MTD of RAD given in combination with the MICE regimen
At one year from study entry
Sergio Amadori, MD
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Italy: Ethics Committee