Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia
Condition: Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and best dose of ixazomib when given in
      combination with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine in
      treating patients with acute myeloid leukemia that is unresponsive to initial induction
      chemotherapy or recurs following an initial complete remission. Acute myeloid leukemia is a
      cancer of the bone marrow cells; bone marrow is where blood cells are normally made. Ixazomib
      may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
      Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, and
      intermediate-dose cytarabine, work in different ways to stop the growth of cancer cells,
      either by killing the cells or by stopping them from dividing. Mitoxantrone hydrochloride,
      etoposide, and intermediate-dose cytarabine are standard treatment for relapsed or refractory
      acute myeloid leukemia. Giving ixazomib with mitoxantrone hydrochloride, etoposide, and
      intermediate-dose cytarabine may improve the effectiveness of the chemotherapy.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and the
      recommended Phase 2 dose of MLN9708 (ixazomib) in combination with mitoxantrone
      hydrochloride, etoposide, intermediate-dose cytarabine (MEC) in patients with relapsed/
      refractory acute myeloid leukemia (AML).

      SECONDARY OBJECTIVES:

      I. To describe the non-dose limiting toxicities associated with MLN9708 in combination with
      MEC in patients with relapsed/ refractory AML.

      II. To describe any preliminary evidence of clinical activity of this combination (compete
      response [CR] rate) in relapsed/ refractory AML.

      III. To determine the median cluster of differentiation (CD)74 antigen expression in patients
      achieving a response versus those patients not achieving a response.

      IV. To determine if gene expression profile pre- and post-treatment correlates with response
      to therapy.

      OUTLINE: This is a dose-escalation study of ixazomib.

      Patients receive ixazomib orally (PO) on days 1, 4, 8, and 11, mitoxantrone hydrochloride
      intravenously (IV), etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6
      hours on days 1-6.

      After completion of study treatment, patients are followed up for 4-5 weeks.
    

Intervention name(s): ixazomib; mitoxantrone hydrochloride; etoposide; cytarabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Given PO; Given IV; Given IV; Given IV
Other intervention name(s): MLN9708; proteasome inhibitor MLN9708; CL 232315; DHAD; DHAQ; Novantrone; EPEG; VP-16; VP-16-213; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside
Intervention MeSH terms: Cytarabine; Etoposide; Mitoxantrone; Etoposide phosphate; Ixazomib; Glycine; Proteasome Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment