Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

• Status: Active, not recruiting
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial is studying the side effects and best dose of veliparib when given together with topotecan hydrochloride with or without carboplatin in treating patients with relapsed or refractory acute leukemia, high-risk myelodysplasia, or aggressive myeloproliferative disorders. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with topotecan hydrochloride and carboplatin may kill more cancer cells.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Carboplatin; Topotecan; Veliparib

Criteria

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