Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML1208)
RATIONALE: Drugs used in chemotherapy, such as mitoxantrone hydrochloride, cytarabine, etoposide, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving everolimus together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with mitoxantrone hydrochloride, cytarabine, etoposide, and idarubicin in treating older patients with newly diagnosed acute myeloid leukemia.
Drug: mitoxantrone hydrochloride
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- 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.
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
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.
- 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.
- 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.
|Ematologia con trapianto- AOU Policlinico Consorziale di Bari|
|Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia|
|Università La Sapienza|
|Roma, Italy, 00100|
|Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia|
|Azienda Ospedaliera Universitaria Policlinico Tor Vergata|
|Rome, Italy, 00133|
|Principal Investigator:||Sergio Amadori, MD||Azienda Ospedaliera Universitaria Policlinico Tor Vergata|