Filgrastim, Cladribine, Cytarabine, and Mitoxantrone With Sorafenib in Treating Patients With Newly-Diagnosed, Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Condition: Acute Biphenotypic Leukemia; Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Myeloproliferative Neoplasm
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte
      colony-stimulating factor [G-CSF]), cladribine, cytarabine, and mitoxantrone, when given
      together with sorafenib and to see how well they work in treating patients with
      newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be
      more aggressive). Drugs used in chemotherapy, such as cladribine, cytarabine, and
      mitoxantrone work in different ways to stop the growth of cancer cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Colony-stimulating
      factors, such as filgrastim, may increase the production of blood cells and may help the
      immune system recover from the side effects of chemotherapy. Sorafenib may stop the growth of
      cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim,
      cladribine, cytarabine, and mitoxantrone together with sorafenib may kill more cancer cells.
    

Detailed description: 
      OUTLINE: This is a phase I, dose-escalation study of mitoxantrone and sorafenib followed by a
      phase II study.

      INDUCTION: Patients receive mitoxantrone intravenously (IV) over 60 minutes on days 1-3 and
      sorafenib orally (PO) twice daily (BID) on days 10-19 in the absence of disease progression
      or unacceptable toxicity. Patients also receive filgrastim subcutaneously (SC) once daily
      (QD) on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2
      hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients
      achieving partial remission (including MRD positive [pos] CR, CR with incomplete platelet
      recovery [CRp], and CR with incomplete count recovery [CRi]) or persistent AML may receive up
      to 2 cycles of induction therapy per the discretion of the treating physician.

      POST-REMISSION: Patients receive sorafenib PO BID on days 8-27 or 3 days prior to next cycle
      of treatment, whichever occurs first. Patients also receive filgrastim subcutaneously SC QD
      on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on
      days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving
      MRDneg CR may receive up to 4 cycles of post-remission therapy. Patients achieving disease
      response (MRDpos CR, CRi/CRp, or persistent disease) may receive up to two induction cycles
      and 1 cycle of post-remission therapy with mitoxantrone omitted in cycle 3. If they then
      enter MRDneg CR, they can proceed with up to a total of 4 cycles of post-remission therapy.

      MAINTENANCE THERAPY: Patients achieving MRDneg CR may receive maintenance therapy of
      sorafenib PO BID for up to 1 year.

      After completion of study treatment, patients are followed up every 3 months for up to 5
      years.
    

Intervention name(s): Cladribine; Cytarabine; Filgrastim; Laboratory Biomarker Analysis; Quality-of-Life Assessment; Mitoxantrone; Sorafenib
Intervention type(s): Drug; Drug; Biological; Other; Other; Drug; Drug
Intervention description(s): Given IV; Given IV; Given SC; Correlative studies; Ancillary studies; Given IV; Given PO
Other intervention name(s): 2-CdA; 2CDA; CdA; Cladribina; Leustat; Leustatin; Leustatine; RWJ-26251; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; FILGRASTIM, LICENSE HOLDER UNSPECIFIED; G-CSF; Neupogen; r-metHuG-CSF; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Nivestym; Filgrastim-aafi; Quality of Life Assessment; Dihydroxyanthracenedione; Mitozantrone; 284461-73-0; BAY 43-9006; Bay-439006
Intervention MeSH terms: Cytarabine; 2-chloro-3'-deoxyadenosine; Sorafenib; Mitoxantrone; Cladribine; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment