A Phase I Study of ABT-888 in Combination With Topotecan Plus Carboplatin for High-Risk Myeloproliferative Disorders and AML Out of Myeloproliferative Disorders

Inclusion Criteria:

- Pathologically confirmed diagnosis of 1 of aggressive MPD or AML out of MPD

- Aggressive phase high-risk myeloproliferative disorders (i.e., polycythemia vera,
essential thrombocythemia, or Ph-negative chronic myelogenous leukemia) meeting ≥ 1
of the following criteria:

- Marrow blasts > 5%

- Peripheral blood blasts plus progranulocytes > 10%

- New onset or increasing myelofibrosis OR;

- New onset or > 25% increase in hepatomegaly or splenomegaly

- New onset constitutional symptoms (i.e., fever, weight loss, splenic pain, or bone
pain)

- Patients who failed primary induction therapy or relapsed after achieving complete
remission are eligible

- No active CNS leukemia; patients with a history of CNS disease must be stable for > 3
months after treatment and off steroid treatment prior to study enrollment

- Chronic myelomonocytic leukemia meeting either of the following criteria:

- 5-19% bone marrow blasts (aggressive)

- At least 20% marrow blasts (transformation)

- ECOG performance status 0-2

- No hyperleukocytosis with >= 50,000 blasts/uL

- AST, ALT, and alkaline phosphatase =< 5 times upper limit of normal

- Bilirubin =< 2.0 mg/dL

- Creatinine normal OR creatinine clearance >= 60 mL/min

- LVEF >= 45% by MUGA or ECHO

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 30 days after
completion of study therapy

- No active disseminated intravascular coagulation

- No active uncontrolled infection

- Patients with infection that is under active treatment and controlled with
antibiotics are eligible

- No other life-threatening illness

- No mental deficits and/or psychiatric history that would preclude giving informed
consent or following protocol

- No prior or current seizure disorder or a history of seizure

- No more than 3 prior cytotoxic regimens

- At least 3 weeks since prior cytotoxic chemotherapy

- At least 2 weeks since prior radiotherapy

- At least 4 weeks since prior autologous or allogeneic stem cell transplantation

- No active graft-versus-host disease

- At least 1 week since prior biologic therapies, including hematopoietic growth
factors

- At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic
trioxide, interferon, or other noncytotoxic agents for blast count control

- No prior ABT-888

- No other concurrent chemotherapy, radiotherapy, or immunotherapy

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent investigational or commercial agents or therapies for this cancer