Safety Study of ABT-888 Plus Topotecan Hydrochloride to Treat Patients With Solid Tumors and Lymphomas

-INCLUSION CRITERIA:

1. Patients with histologically documented solid tumors and lymphoid malignancies (lymphoma and CLL) who are refractory to standard therapy or who have no acceptable standard treatment options. Patients with lymphoid malignancies will be eligible if their disease has progressed following standard therapy and if stem cell transplantation is not indicated or has been refused.
2. Any prior therapy must have been completed greater than or equal to 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels (CTCAE Grade less than or equal to 1) from prior toxicity. Prior radiation or surgery should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study, and should have recovered to eligibility levels from any toxicities.
3. Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of ABT-888 in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.
4. ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).
5. Life expectancy of greater than 3 months.

6. Patients must have normal organ and marrow function as defined below:

   • absolute neutrophil count greater than or equal to 1,500/mcL
   • platelets greater than or equal to 100,000/mcL
   • total bilirubin less than 1.5 times institutional upper limit of normal
   • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
   • creatinine less than 1.5 times institutional upper limit of normal

   OR

   -creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal.

7. The effects of ABT-888 on the developing human fetus are unknown. For this reason and because topotecan hydrochloride used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after completion of study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
8. Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study, and should have recovered to eligibility levels from any toxicities.

   Patients who have been administered ABT-888 as part of a single or limited dosing study, such as a Phase 0 study, should not be excluded from participating in this study solely because of receiving prior ABT-888.

   Patients who have received prior TPT should not be excluded solely because of receiving prior TPT.

2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, prolonged QTc interval (greater than msec), or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patients with known brain mestastases or a history of seizures are excluded from this clinical trial.