• Maximum tolerated dose and dose-limiting toxicity of ABT-888 and cyclophosphamide [ Designated as safety issue: Yes ]
  

• Pharmacokinetic parameters [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To identify the maximum tolerated dose and dose-limiting toxicity of ABT-888 when administered in combination with cyclophosphamide in patients with metastatic or unresectable solid tumors or non-Hodgkin lymphoma.

Secondary

• To evaluate the effect of ABT-888 on the systemic clearance of cyclophosphamide and the dose-normalized AUC of its 4-OH metabolite.
• To evaluate the effect of cyclophosphamide on the systemic pharmacokinetics of ABT-888 and its primary metabolite A-925088.
• To evaluate poly (ADP ribose) polymerase (PARP) enzyme inhibition using an immunoassay designed to measure poly-ADP-ribosylated (PAR) levels in peripheral blood mononuclear cell samples at baseline and during study treatment.

OUTLINE: Patients receive oral ABT-888 twice daily on days 1-4 and cyclophosphamide IV over 60 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic analysis by liquid and gas chromatography and mass spectrometry assays and for analysis of poly-ADP-ribosylated (PAR) levels by immunoassay.

After completion of study treatment, patients are followed for 4 weeks.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor or non-Hodgkin lymphoma (NHL)*

  • Metastatic or unresectable disease NOTE: *Patients with NHL amenable to hematopoietic stem cell transplantation with curative intent are eligible only if stem cell transplant is refused or is not indicated
• Standard curative or palliative measures do not exist or are no longer effective

• No active CNS metastases

  • Previously treated CNS metastases allowed provided patient is asymptomatic and off steroids for > 2 months

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 2 months
• Hemoglobin ≥ 9.0 g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,00/mm³
• Total bilirubin normal
• AST or ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if hepatic metastases are present)
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• PT/INR or PTT ≤ 1.2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • New York Heart Association class II-IV congestive heart failure
  • Cardiac arrhythmia
  • Unstable angina pectoris
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No condition (e.g., active peptic ulcer disease or gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation) that would impair the ability to swallow and retain ABT-888 capsules
• No malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, partial or complete small bowel obstruction, or other disease significantly affecting gastrointestinal function
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to ABT-888 and/or cyclophosphamide
• No known history of seizures or seizure disorder
• No other significant medical, social, or psychological condition that may significantly affect safety and/or study compliance
• HIV seropositivity allowed provided CD4 count ≥ 350/mm³ AND there are no opportunistic infections

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin C) or radiotherapy
• At least 7 days since prior and no concurrent strong inhibitors or strong inducers of CYP3A4 (including grapefruit or grapefruit juice), CYP2B6, CYP2C9, or CYP2C19 (≥ 6 months for amiodarone)
• No prior high-dose therapy requiring hematopoietic stem cell transplantation
• No prior anticancer radioactive pharmaceutical treatment
• No prior stomach or small bowel resection or other surgical procedures affecting absorption
• No concurrent prophylactic hematopoietic growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or interleukin-11) during the first course of study treatment
• No concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients