3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Polycythemia Vera; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Hypereosinophilic Syndrome; Philadelphia Chromosome
Intervention: fludarabine phosphate; triapine; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative study
Intervention MeSH terms: Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving 3-AP together with fludarabine works in
      treating patients with myeloproliferative disorders (MPD), chronic myelomonocytic leukemia
      (CMML), or accelerated phase or blastic phase chronic myelogenous leukemia. Drugs used in
      chemotherapy, such as 3-AP and fludarabine, work in different ways to stop the growth of
      cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help
      fludarabine work better by making cancer cells more sensitive to the drug. 3-AP and
      fludarabine may also stop the growth of cancer cells by blocking some of the enzymes needed
      for cell growth. Giving 3-AP together with fludarabine may kill more cancer cells.
    

Eligibility criteria:

        Criteria:

          -  Not pregnant or nursing

          -  Histopathologically confirmed diagnosis of 1 of the following:

               -  Myeloproliferative disorders (MPDs) in aggressive phase or transformation

               -  CML in accelerated phase or blast crisis

               -  Chronic myelomonocytic leukemia in aggressive phase (5-19% bone marrow blasts) or
                  transformation (> 20% bone marrow blasts)

          -  Myeloproliferative disorders (MPDs) in aggressive phase or transformation, including
             the following:

               -  Polycythemia vera (PV)

               -  Essential thrombocythemia (ET)

               -  Myelofibrosis with myeloid metaplasia

               -  Hypereosinophilic syndrome

               -  Atypical (Philadelphia chromosome negative) chronic myelogenous leukemia (Ph-
                  CML)

          -  Patients with aggressive phase MPD (PV, ET, or Ph- CML) must meet ≥ 1 of the following
             criteria:

               -  Marrow blasts > 5%

               -  Peripheral blood blasts plus progranulocytes > 10%

               -  New onset or increasing myelofibrosis

               -  New onset or > 25% increase in hepatomegaly or splenomegaly

               -  New onset constitutional symptoms (fever, weight loss, splenic pain, bone pain)

          -  Multilineage bone marrow failure

          -  Ineligible for established curative regimens, including stem cell transplantation

          -  ECOG performance status 0-2

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No chronic toxicity from prior chemotherapy > grade 1

          -  No history of severe coronary artery disease

          -  Creatinine normal OR creatinine clearance >= 60 mL/min

          -  AST and ALT =< 2.5 times normal

          -  Bilirubin =< 2.0 mg/dL unless due to leukemia, Gilbert's syndrome, or hemolysis

          -  No arrhythmias (other than atrial flutter or fibrillation) requiring medication

          -  No uncontrolled congestive heart failure

          -  No dyspnea at rest or with minimal exertion

          -  No severe pulmonary disease requiring supplemental oxygen

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to 3-AP (Triapine®) and/or fludarabine phosphate

          -  No other life-threatening illness

          -  No history of mental deficits and/or psychiatric illness that would preclude study
             compliance

          -  No more than 4 prior induction regimens (3 cytotoxic chemotherapy regimens)

          -  At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin
             C or nitrosoureas) and recovered

          -  At least 1 week since prior nonmyelosuppressive treatment

          -  At least 48 hours since prior noncytotoxic agents for peripheral blood leukemic cell
             count control, including but not limited to the following:

               -  Hydroxyurea

               -  Imatinib mesylate

               -  Interferon

               -  Mercaptopurine

               -  Cyclophosphamide

          -  At least 2 weeks since prior and no concurrent radiotherapy to treat cancer

          -  At least 1 week since prior biologic therapy, including hematopoietic growth factors
             (e.g., epoetin alfa, darbepoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF],
             interleukin-3, or interleukin-11)

          -  No other concurrent chemotherapy to treat cancer

          -  No concurrent immunotherapy to treat cancer

          -  No known glucose-6-phosphate dehydrogenase [G6PD) deficiency (G6PD screening required
             for high-risk groups (i.e., patients of African, Asian, or Mediterranean
             origin/ancestry)]

          -  No active heart disease

          -  No concurrent myeloid growth factors

          -  No active uncontrolled infection (Infections under active treatment and controlled
             with antibiotics are allowed)

          -  No chronic hepatitis