3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia

• Status: Completed
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Fludarabine; Fludarabine phosphate; Vidarabine

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