Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia
Condition: 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 Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide, and
      cytarabine, work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping them from dividing. Giving bortezomib together with combination
      chemotherapy may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when
      given together with mitoxantrone, etoposide, and cytarabine in treating patients with
      relapsed or refractory acute myeloid leukemia.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the DLT, MTD, and the recommended Phase 2 dose of bortezomib in combination
      with MEC in patients with relapsed/refractory AML.

      SECONDARY OBJECTIVES:

      I. To describe the non-dose limiting toxicities associated with bortezomib in combination
      with MEC in patients with relapsed/refractory AML.

      II. To describe any preliminary evidence of clinical activity of this combination (CR rate)
      in relapsed/refractory AML.

      III. To determine the median CD74 antigen expression in patients achieving a response versus
      those patients not achieving a response.

      OUTLINE:

      This is a dose-escalation study of bortezomib.

      Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11; and mitoxantrone IV,
      etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6.
      Treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 4-5 weeks.
    

Intervention name(s): bortezomib; mitoxantrone hydrochloride; etoposide; cytarabine; flow cytometry
Intervention type(s): Drug; Drug; Drug; Drug; Other
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Correlative studies
Other intervention name(s): LDP 341; MLN341; PS-341; VELCADE; CL 232315; DHAD; DHAQ; dihydroxyanthracenedione; mitoxantrone HCl; Novantrone; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; epipodophyllotoxin; VePesid; VP-16; VP-16-213; ARA-C; ARA-cell; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside
Intervention MeSH terms: Cytarabine; Etoposide; Podophyllotoxin; Mitoxantrone; Etoposide phosphate; Bortezomib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment