RTA 744 Injection in Patients With Leptomeningeal Disease

Inclusion Criteria:

1. Age \>/=18 years.
2. Histologic confirmation of primary malignancy at original diagnosis. All primary tumor types may be enrolled into the study (solid tumor, lymphoma, leukemia, or brain malignancy).
3. Neoplastic meningitis/leptomeningeal metastasis refractory to conventional intrathecal therapy and defined as presence of tumor cells on cytology after cytospin, OR neuroimaging evidence of leptomeningeal tumor by MRI accompanied by clinical evidence of leptomeningeal tumor.
4. Patient is not eligible for higher priority clinical trial.
5. If patient had surgical resection prior to enrollment, at least 2 weeks should have elapsed prior to enrollment into the study and patient must have completely recovered from the side effects of such therapy.
6. For those patients taking steroid medications, the dose of steroid should be stable for at least 7 days prior to obtaining the Gd-MRI of the brain and spine, if medically feasible.
7. Karnofsky Performance Status (KPS) of \>/= 60.
8. Laboratory Parameters: 1) Absolute Neutrophil Count (ANC) \>/=1.5 x 10\^9/L; 2) Hemoglobin (Hgb) \>/=9 g/dl; 3) Platelets \>/= 100 x 10\^9/L; 4) AST and ALT \</= 3.0 x Upper Limit of Normal (ULN); 5) Serum bilirubin \</= 1.5 x ULN; 6) Serum creatinine \</= 1.5 x ULN and 24 hour creatinine clearance \>/= 50 ml/min
9. Life expectancy of at least 8 weeks based on the judgment of the clinical investigator.
10. Written informed consent obtained.

Exclusion Criteria:

1. Concurrent intrathecal or intraventricular therapy for leptomeningeal disease or other malignancy.
2. Concurrent oral or intravenous cytotoxic therapy for leptomeningeal disease or other malignancy. Patients who are receiving non-cytotoxic concurrent drug for their malignancy may be allowed on the study, provided that the non-cytotoxic drug was started for at least 4 weeks prior to entry into the study and that no apparent toxicity from the non-cytotoxic drug is evident.
3. Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
4. Patient has previously received anthracycline therapy up to the following cumulative doses: doxorubicin \>/= 550 mg/m\^2 (\>/= 450 mg/m\^2 if patient has had prior chest radiotherapy), epirubicin \>/= 1000 mg/m\^2 (\>/= 800 mg/m\^2 if prior chest radiation), idarubicin \>/= 150 mg/m\^2 (\>/= 130 mg/m\^2 if prior chest radiotherapy) and daunorubicin \>/= 550 mg/m\^2 (\>/= 400 mg/m\^2 if prior chest radiotherapy).
5. Patients on anticonvulsant medications or other types of medications which are known liver-enzyme inducers.
6. Patients who are pregnant or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control (such as oral, implantable, or injectable contraceptives ) (Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of RTA 744 Injection)
7. Total urinary protein in 24 hours urine collection \> 500 mg
8. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1) Uncontrolled diabetes (patients diagnosed with Type 1 or Type 2 diabetes who are currently under treatment by a physician for this condition and are not able to control blood sugars with management for glucose levels above 250 mg/dL). 2) Active or uncontrolled infection. 3) Acute or chronic liver disease (i.e., hepatitis, cirrhosis). 4) Confirmed diagnosis of HIV infection
9. Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type, including any of the following: 1) LVEF \< 45% as determined by MUGA scan or echocardiogram. 2) Complete left bundle branch block. 3) Obligate use of a cardiac pacemaker. 4) ST depression of \> 1mm in \>/= 2 leads and/or T wave inversions in \>/= 2 contiguous leads. 5) Congenital long QT syndrome.
10. 9\. (continued) 6) History or presence of ventricular or atrial tachyarrhythmias. 7) Clinically significant resting bradycardia (\< 50 beats per minute). 8) QTc \> 480 msec on screening ECG. 9) Uncontrolled high blood pressure(\>140/90), history of labile hypertension, or history of poor compliance with an antihypertensive regimen. 10) Unstable angina pectoris. 11) Symptomatic congestive heart failure.
11. Myocardial infarction \</=6 months prior to starting study drug. Patients with a history of CHF or arrhythmias
12. Patients who are taking therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed.)
13. Patients who have received the following types of prior or concurrent therapy, or who have not recovered from the toxic effects of such therapy: 1) investigational drugs less than 4 weeks prior to entry on this study. 2) intrathecal chemotherapy within 2 weeks prior to entry into this study. 3) systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine) to entry on this study. 4) radiation therapy within 2 weeks prior to entry on this study. 5) any medication known to cause QT interval prolongation.
14. Patients who have had any surgery, including resection of a brain tumor within 2 weeks prior to entry on this study
15. Patients unwilling to or unable to comply with the protocol
16. Patients who have a contraindication to MRI imaging (cardiac pacemaker, other ferromagnetic metal implants, claustrophobia not amenable to conscious sedation, and obesity greater than 300 lbs).