Higher or Lower Dose Cladribine, Cytarabine, and Mitoxantrone in Treating Medically Less Fit Patients With Newly Diagnosed Acute Myeloid Leukemia or Myeloid Neoplasm
Condition: Acute Leukemia of Ambiguous Lineage; Acute Myeloid Leukemia; Myeloid Neoplasm
MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Cladribine; Cytarabine; Granulocyte Colony-Stimulating Factor; Mitoxantrone Hydrochloride; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given IV; Given IV; Given SC; Given IV; Ancillary studies; Ancillary studies
Intervention MeSH terms: Cytarabine; 2-chloro-3'-deoxyadenosine; Mitoxantrone; Cladribine; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and
      mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid
      leukemia or myeloid neoplasm. 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. It is not yet
      known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may
      work better in treating patients with newly diagnosed acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of untreated "high-grade" myeloid neoplasm (>= 10% myeloid blasts by
             morphology in bone marrow and/or peripheral blood) or AML other than acute
             promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016
             World Health Organization (WHO) classification; patients with acute leukemias of
             ambiguous lineage are eligible; outside diagnostic material is acceptable as long as
             peripheral blood and/or bone marrow slides are reviewed at the study institution and
             cytogenetic/molecular information is available

          -  Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model

          -  The use of hydroxyurea before enrollment is permitted; hydroxyurea should be
             discontinued prior to start of study treatment. Patients with symptoms/signs of
             leukostasis, white blood cell (WBC) > 100,000/uL, or acute symptoms felt related to
             their high-grade myeloid neoplasm can be treated with leukapheresis or may receive up
             to 1 dose of cytarabine (up to 500 mg/m^2) anytime prior to study day 1

          -  Patients may have received treatment (e.g. azacitidine/decitabine, lenalidomide,
             growth factors) for antecedent low-grade myeloid neoplasm

          -  Left ventricular ejection fraction (LVEF) >= 45%, assessed within 3 months prior to
             registration, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other
             appropriate diagnostic modality

          -  Women of childbearing potential and men must agree to use adequate contraception
             beginning at the signing of the consent until at least 4 weeks after the last dose of
             study drug

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not
             considered candidate for tyrosine kinase inhibitor treatment

          -  Concomitant illness associated with a likely survival of < 1 year

          -  Active systemic fungal, bacterial, viral, or other infection, unless disease is under
             treatment with anti-microbials and/or controlled or stable; patients with fever
             thought to be likely secondary to leukemia are eligible; known hypersensitivity to any
             study drug

          -  Known hypersensitivity to any study drug used in this trial

          -  Pregnancy or lactation

          -  Concurrent treatment with any other anti-leukemia agent