Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): cytarabine; etoposide; everolimus; idarubicin; mitoxantrone hydrochloride
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.; Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.; 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.; Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.; Remission induction therapy: by short i.v. infusion on days 1, 3 and 5
Other intervention name(s): Mini-ICE regimen (idarubicin, cytarabine and etoposide).; Mini-ICE regimen (idarubicin, cytarabine and etoposide).; RAD001; Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Intervention MeSH terms: Cytarabine; Etoposide; Mitoxantrone; Idarubicin; Etoposide phosphate; Everolimus; Ifosfamide; Carboplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)