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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 25.0-80.0, Benign Prostatic Hyperplasia (BPH) Urinary Retention Urinary Hesitancy Intermittent Male subjects 25-80 years of age at the screening visit Subject must have mild-to-moderate urinary hesitancy symptoms (shown as an American Urological Association Symptom Index (AUA-SI) score of 7-19) Symptoms (not limited to) Leaking or dribbling of urine More frequent urination, especially at night Urgency to urinate Urine retention (inability to urinate) Hesitant, interrupter or weak stream of urine Inability or difficulty to urinate in public History of prostate cancer or prostate surgery Currently (or within the past 30 days) on active treatment for prostate problems

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Varicose Veins All patients with varicose veins who underwent endovenous laser treatment for GSV reflux in our hospital were reviewed poor general health, inability to walk, active inflammation of varicose veins, deep venous occlusion disease, hypercoagulability, pregnancy and breast-feeding

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Mixed Gliomas Malignant Gliomas Glioblastoma Multiforme Histologically confirmed intracranial Grade 3 or 4 anaplastic glioma or glioblastoma (astrocytic tumor, anaplastic oligodendroglioma, or oligoastrocytoma) Received prior standard radiation for a Grade 3 or 4 astrocytic tumor with a minimum cumulative dose of 40 Gy administered Completed at least one full cycle of temozolomide of 200 mg/m2/day administered on Days 1-5 of a 28-day cycle, without unacceptable toxicity or progression Karnofsky performance status of 60 or more Adequate organ and bone marrow function as defined by hematological and serum chemistry limits At least 18 years old Both men and women must practice adequate contraception Informed consent Progressed while on temozolomide Evidence of acute intracranial or intratumoral hemorrhage > Grade 1 Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including cytotoxic chemotherapy other than temozolomide, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents, prior therapy with a PI3K inhibitors, radiation therapy, enzyme-inducing anti-convulsants, valproic acid Not recovered from the toxic effects of prior therapy Pregnant or breast feeding History of diabetes mellitus Uncontrolled intercurrent illness Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study HIV positive Diagnosis of another malignancy may subject from study

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Glioma Astrocytoma All patients treated with temozolomide for newly diagnosed malignant glioma (concomitant with radiotherapy and then as monotherapy) and relapsed malignant glioma (as monotherapy) Patients with a history of hypersensitivity to temozolomide or dacarbazine Pregnant women and women who may be pregnant

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Oligodendroglioma Oligoastrocytoma written informed consent centrally confirmed anaplastic glioma according to the WHO-classification 1998/2000 age ≥ 18 years Karnofsky performance status (KPS) of 70 or higher no prior systemic chemotherapy or radiation therapy of the brain no HIV infection adequate bone marrow reserve, liver function, and renal function Patients on corticosteroids had to be on a stable or decreasing dosage within the 14 days prior to randomization Glioblastoma infratentorial localization of the tumor pregnancy or lactation period serious medical or neurological comorbidity additional malignancy requiring radio or chemotherapy known hypersensitivity against study drugs inability to swallow frequent emesis psychological. familial, sociological or geographical situations impairing compliance with F/U examinations

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain and Central Nervous System Tumors Newly diagnosed grade III or IV glioma including any of the following Glioblastoma Anaplastic astrocytoma Gliosarcoma Anaplastic oligodendroglioma Anaplastic oligoastrocytoma Measurable or nonmeasurable disease No more than 5 weeks since prior brain surgery Recovered from surgery, post operative infection, and other complications

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Glioblastoma Glioma Astrocytoma Participants who are prescribed with temozolomide by local labeling participants with newly diagnosed glioblastoma multiforme participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy N/A

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Patients with histologically proven intracranial malignant glioma are eligible . -All patients must sign an informed consent Patients must be > 18 years old, and with a life expectancy > 8 weeks Patients must have a Karnofsky performance status of > 60 Patients must have recovered from the toxic effects of prior therapy Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL and/or creatinine clearance > 60 cc/min) Patients must have shown radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. -Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply They have recovered from the effects of surgery Residual disease following resection of recurrent malignant glioma is not mandated for into the study Patients must have failed prior radiation therapy Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration Patients must not have any significant medical illnesses that in the investigator opinion cannot be adequately controlled Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible Patients must not have active infection or serious intercurrent medical illness Patients must not be pregnant/breast feeding and must agree to practice adequate contraception Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism Patients must not have received prior therapy with irinotecan Patients with 7/7 (homozygous) UGT1A1*28 genotyping will be excluded from the study Patients receiving enzyme-inducing anticonvulsants or other enzyme inducing drugs are excluded

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Glioma Patients must have a histologically confirmed diagnosis of a recurrent/progressive WHO Gr.4 malignant glioma (glioblastoma multiforme or gliosarcoma) or WHO Gr.3 malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma). Recurrence will be defined based on the modified MacDonald or based on histopathologic confirmation of tissue obtained via surgical intervention. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Gr.III or IV malignant glioma; 2. > or = to 18 y/o; 3. KPS . or = to 60%; 4. Patients must be presenting in 1st, 2nd or 3rd relapse. Relapse is defined as progression following anti-cancer therapy other than surgery, including non-surgical therapies that are considered standard treatment for high-grade glioma if administered to patients with prior low-grade glioma. Prior therapy must have included external beam radiotherapy; 5. Adequate bone marrow, liver and renal function as assessed by the following: Hematocrit > or = to 29%, ANC > or = to 1,500/mm3, Platelet count > or = to 125,000/mm3, Total bilirubin < or = to 1.5 x ULN, ALT and AST < or = to 2.5 x the ULN ( < or = to 5 x ULN for patients with liver involvement), INR < 1.5 or a PT/PTT within normal limits (unless on therapeutic anti-coagulation). Patients receiving anti-coagulation treatment with a low-molecular weight heparin will be allowed to participate, however oral warfarin is not permitted except for low-dose warfarin (1mg po DAILY), Creatinine < 1.5 x ULN, Serum Na, K+, Mg2+, Phosphate and Ca2+ > or = to Lower Limit of Normal (LLN); 6. An interval of at least 2 weeks between prior surgical resection (1 week for biopsy) and initiation of study regimen; 7. An interval of at least 12 weeks from completion of standard, daily XRT, unless one of the following occurs: a) new area of enhancement on MRI imaging that is outside the XRT field; b) biopsy proven recurrent tumor; c) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart; 8. An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and the patient has recovered from all anticipated toxicities from prior therapy; 9. An interval of a least 14 days from exposure to investigational agents, unless there is unequivocal evidence of tumor progression and the patients has recovered from all anticipated toxicities from prior therapy; 10. Signed written informed consent including HIPAA according to institutional guidelines. A signed informed consent must be obtained prior to any study specific procedures; 11. If sexually active, patients will take contraceptive measures for the duration of the treatments and for 3 months following discontinuation of dasatinib and TMZ; 12. Women of childbearing potential must have a negative serum or urine pregnancy test (sensitivity < or = to 25IU HCG/L) within 72 hours prior to the start of study drug administration Prior dasatinib. Imatinib mesylate in the prior three months; 2. Grade 3 or greater toxicity related to prior TMZ therapy; 3. Prior progression on protracted daily TMZ; 4. Pregnancy or breast feeding; 5. History of significant concurrent illness; 6. More than 3 prior episodes of progressive disease; 7. Significant cardiac disease including any of the following: 1. congestive heart failure > class II NYHA; 2. unstable angina (anginal symptoms at rest); 3. new onset angina (began within the last 3 months); 4. myocardial infarction within the past 6 months; 5. any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); 6. uncontrolled congestive heart failure; diagnosed congenital long QT syndrome; prolonged QTc interval on pre-entry electrocardiogram (> 450 msec); 8. Excessive risk of bleeding as defined by stroke within the prior 6 months, history of CNS or intraocular bleed, or septic endocarditis; 9. Female patients who are pregnant or breastfeeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of study regimen). Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy; 10. Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study such as pleural or pericardial effusion of any grade, uncontrolled diabetes, uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management), active clinically serious infection > CTCAE Gr.2, history of clinically significant bleeding diathesis or coagulopathy including platelet function disorder (e.g. known von Willebrand's disease) or acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), impairment of GI function or GI disease that may significantly alter the absorption of the study regimen (i.e. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets), ongoing or recent (< or = to 3 months) significant gastrointestinal bleeding; 11. Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months; 12. Any hemorrhage/bleeding event > CTCAE Gr.3 within 4 weeks of 1st dose of study drug; 13. Serious non-healing wound, ulcer, or bone fracture; 14. Major surgery, open biopsy or significant traumatic injury within 4 weeks of 1st study drug; 15. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C; 16. Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed; 17. Patient unwilling to or unable to comply with the protocol including ability to swallow whole pills or presence of any malabsorption syndrome; 18. Concurrent administration of warfarin, rifampin or St. John's Wort, except for low-dose warfarin (1mg po DAILY); 19. Clinically serious infection requiring active intervention (CTCAE Gr.2 or greater); 20. Hypokalemia or hypomagnesemia if it cannot be corrected; 21. Concomitant Medications, consider the following prohibitions: 1. Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) 1. quinidine, procainamide, disopyramide 2. amiodarone, sotalol, ibutilide, dofetilide 3. erythromycin, clarithromycin 4. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide 5. cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. 2. Drugs that reduce dasatinib exposure such as H2 blockers or proton-pump inhibitors (eg famotidine and omeprazole), which can cause long-term suppression of gastric acid secretion. The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is in general not recommended and antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy. However, given that nearly all recurrent malignant brain tumor patients are on dexamethasone for increased intracranial pressure, such patients must also receive effective medical therapy to prevent complications related to increased gastric acid secretion due to chronic dexamethasone therapy. Therefore all patients enrolled on the current protocol will receive standard H2 blocker (preferred) or proton pump inhibitor (PPI) therapy to be administered on a daily basis each evening. Dasatinib will be administered each morning in order to maximize the time interval from administered H2 blocker (preferred) or proton pump inhibitor (PPI). 3. Drugs that cause hypocalcemia (i.e. IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia). 4. Any prohibited CYP3A4 inhibitors; 22. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Lung Cancer Head and Neck Cancer Histologically or cytologically documented diagnosis of advanced/metastatic NSCLC or Head and Neck cancer Male or female patients aged ≥ 18 years old Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed Have progressive and measurable disease that can be measured by Response Evaluation in Solid Tumors (RECIST) Patients must have discontinued prior systemic chemotherapy by 14 days Patients must meet the following laboratory 1. Serum albumin ≥ 3g/dL 2. Aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN)or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement 3. Serum bilirubin ≤ 1.5 x ULN 4. Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min 5. Serum potassium ≥ lower limit of normal (LLN) and ≤ ULN 6. Serum phosphorous ≥ LLN 7. Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN 8. Serum magnesium ≥ LLN 9. Absolute neutrophil count (ANC) (ANC: segmented and bands) ≥ 1.5 X10^9/L 10. Platelets ≥ 100 X 10^9/L Baseline multiple gated acquisition imaging (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study Patient instructed that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of LBH589 therapy due to risk of hypocalcemia Impaired cardiac function including any one of the following: 1. Screening electrocardiogram (ECG) with a corrected QT (QTc) > 450 msec confirmed by central laboratory prior to enrollment to the study 2. Patients with congenital long QT syndrome 3. History of sustained ventricular tachycardia 4. Any history of ventricular fibrillation or torsades de pointes 5. Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible. 6. Patients with a myocardial infarction or unstable angina within 6 months of study entry 7. Congestive heart failure New York Heart Association (NYHA) class III or IV 8. Right bundle branch block and left anterior hemiblock (bifascicular block) 9. Patients with a history of uncontrolled or chronic atrial fibrillation Uncontrolled hypertension, blood pressure (BP) >180/110 on 3 separate occasions despite oral antihypertensive medications Concomitant use of drugs with a risk of causing torsades de pointes Concomitant use of CYP3A4 inhibitors Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic Patients with unresolved diarrhea > Common Terminology for Adverse Events (CTCAE) grade 1 Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 Other concurrent severe and/or uncontrolled medical conditions Patients who have received chemotherapy < 14 days, any investigational drug < 14 days or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy Concomitant use of any anti-cancer therapy (except erlotinib) or radiation therapy

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-999.0, Osteoarthitis Chronic Pain Knee Pain Subjects with a clinical diagnosis of osteoarthritis of the knee based symptoms and/or radiographic present for at least 3 months Moderate to severe chronic pain due to knee osteoarithritis Previously opioid treated subject who had a history of withdrawal after cessation of the opioid History of seizure disorder, psychiatric disease and history of head trauma requiring evaluation by hospital based staff, or unconsciousness of unknown origin. Subjects who, in the investigator's judgment, have well-controlled depression or anxiety disorder may participate Subjects with history of uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg) Intake of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, barbiturates, neuroleptics, monoamine oxidase inhibitors, and antiparkinsonian drugs within the 30 days prior to the screening visit

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Anaplastic Astrocytoma Glioblastoma The patient has provided written informed consent prior to any study-related procedure The patient is at least 18 years of age and equal to or below 70 years The patient has a present diagnosis of AA or secondary GBM The patient has a measurable lesion (> 1 ccm in volume, central MRI review) The lesion (or sum of lesions) does not exceed 50 ccm in volume (central MRI review) The tumor is localized supratentorially (central MRI review) All patients have recurrent or refractory disease, i.e. disease has progressed after prior surgery and radiotherapy at any time of the disease course or stage. Secondary GBM patients have progressed after a previous diagnosis of A and/or AA The patient has not received more than one chemotherapy regimen. Radiation with concomitant chemotherapy, followed by adjuvant chemotherapy, is considered as one chemotherapy regimen The patient is eligible for chemotherapy The patient is on a maximum dose of 4 mg/day dexamethasone or equivalent doses for other corticosteroids, which has been stable or decreasing for at least 3 weeks prior to Screening Patient unable or not willing to comply with the protocol regulations The investigator deems it necessary to surgically (re-)resect the present tumor (NOTE: the patient might still be eligible for randomization at a later timepoint) Tumor surgery, tumor debulking, or other neurosurgery within 3 months prior to randomization. If a ≤48-hour routine post-surgery MRI (in accordance with study specifications) qualifies the patient for study participation, the patient can be randomized 30 ± 7 days post-surgery Radiotherapy or stereotactic (gamma knife) radiosurgery within 3 months prior to randomization Prior interstitial brachytherapy of the brain with permanent implants. Prior interstitial brachytherapy of the brain with removable implants within 3 months prior to randomization Chemotherapy, hormone therapy, or any other therapy with established or suggested anti-tumor effects within 4 weeks (nitrosoureas: 6 weeks) prior to randomization Prior anti-TGF-beta 2 targeted therapy Screening MRI shows a mass effect caused by the tumor defined as significant compression of the ventricular system and/or a midline shift (≥ 3 mm, central MRI review). Compression of the ventricular system and/or a midline shift ≥ 3 mm only due to the presence of (a) cyst(s) or scarring processes does not an individual from the study Participation in another clinical study with another investigational medicinal product within 30 days prior to randomization History of a second independent malignant disorder within 5 years, except for carcinoma in situ of the cervix and basal cell carcinoma

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Astrocytoma Subject must have histologically confirmed anaplastic astrocytoma on the tentorium at first relapse, and satisfy the following unequivocal evidence of tumor recurrence or aggravation by MRI scan after treatment for initial onset; the lesions must be measurable anaplastic astrocytoma diagnosed histologically by the last pathological diagnostic tests (including initial diagnosis) prior to initial administration of temozolomide tissue samples available for Central Pathologic Reviewer pathologic diagnosis report by the study-conducting medical institution must be available for the sponsor MRI-related MRI scan performed within 14 days before initial temozolomide administration assessable tumor site confirmed by MRI dosage of steroidal agents not increased within 7 days before MRI prior to initial temozolomide administration, except for postoperative subjects for first relapse MRI performed at the Principal Investigator's study location or designated radiology facility during the study History of treatment with dacarbazine Subjects who received chemotherapy within 6 weeks before initial temozolomide administration Subjects who received interstitial radiotherapy or stereotactic radiosurgery Subjects who completed radiotherapy within 12 weeks before initial temozolomide administration Surgery at first relapse (including biopsy) within 1 week before initial temozolomide administration Subjects not recovered from acute toxicity due to previous therapy High-risk subjects with complication of diseases other than malignant tumor, or who require systemic administration of antibiotics for infection Previous or concurrent malignancies at other sites Pregnant or nursing women Women of childbearing potential not using an effective method of contraception

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Neuroblastoma Patients with high-risk neuroblastoma Patients with intermediate-risk neuroblastoma if gross tumor remained after surgery Patients with progressive disease before high-dose chemotherapy Patients whose parents want to stop or change the planned treatment Patients with organ toxicities of NCI grade >2 before high-dose chemotherapy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Urinary Catheterization Male patients Urinary retention defined as >150cc retained in bladder on post void residual Female patients Known urethral stricture Active symptomatic Urinary Tract Infection History of pelvic fracture or urethral disruption History of previous urethroplasty(urethral reconstructive surgery) Known Latex allergy Unable to physically perform CIC Unable to provide follow up Unable to give consent Currently taking chronic narcotic pain medication

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme/Anaplastic Astrocytoma Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal Age > 18 years Given written consent Adequate bone marrow reserve(hemoglobin > 10 grams, Absolute neutrophil count > 1500 / mm3, platelets > 100,000/ mm3) Normal renal function(BUN < 24 mg/dL, Creatinine < 1.3 mg/dL) Normal liver function(Total Bilirubin < 1.5 mg/dL, SGPT/ALT < 60 U/L) Have a Karnofsky score of < 60 [Appendix B] or age < 18 years Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma Tumors located in the brainstem or optic chiasm Prior radiation therapy to the brain Prior chemotherapy within the past 6 weeks

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 3.0-75.0, Accelerated Phase Chronic Myelogenous Leukemia Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Aplastic Anemia Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia de Novo Myelodysplastic Syndromes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Fanconi Anemia Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Paroxysmal Nocturnal Hemoglobinuria Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Splenic Marginal Zone Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Small Lymphocytic Lymphoma Waldenström Macroglobulinemia Diagnosis of a histology documented hematologic malignancy or marrow disorder Bone marrow failure disorders and other non-malignant hematologic or immunologic disorders Acquired bone marrow failure disorders aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) Primary allogeneic hematopoietic stem cell transplantation (HSCT) is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available Patients with PNH must have a history of thrombosis related to PNH Hereditary bone marrow failure disorders Fanconi anemia or related chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable Dyskeratosis: diagnosis is supported by using either telomerase reverse transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked DKC1 gene mutation Other non-malignant hematologic or immunologic disorders that require transplantation Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia) Uncontrolled central nervous system (CNS) disease (for hematologic malignancies) Karnofsky (adult) or Lansky (for =< 16 years) performance status =< 50% Diffusing capacity of the lung for carbon monoxide (DLCO) less than 40% predicted, corrected for hemoglobin (Hb) and/or alveolar ventilation Cardiac: left ventricular ejection fraction less than 40% Bilirubin >= 3 x upper limit of normal Liver alkaline phosphatase >= 3 x upper limit of normal Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) >= 3 x upper limit of normal Child's class B and C liver failure Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics Patients who have received maximally allowed doses (given in 2 Gy fractions, or equivalent) of previous radiation therapy to various organs as follows

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Cancer A new diagnosis of a primary glioma, astrocytoma, oligodendroglioma, oligo-astrocytoma, ependymoma, tanycytic ependymoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligo-astrocytoma, anaplastic ependymoma 2. Radiation therapy as part of the plan of care 3. Age >/= 18 years of age. Children are excluded from this study because of differences in tumor location and biology with differing symptom clusters. A separate study will be conducted in the future with children. 4. Ability to speak, write, and read English 5. On corticosteroids at the initiation of radiation therapy Tumors involving the suprasellar region, including the pituitary and hypothalamus 2. Cognitive deficits which limit ability to self-report symptoms

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Anaplastic Oligodendroglioma Histological documentation of newly diagnosed malignant glioma ECOG performance status of 0 or 1 Age ≥18 Life expectancy of at least 12 weeks Hemoglobin ≥ 9.0 g/dl Granulocyte count ≥1.5 X 10^9/L Platelet count ≥100 X 10^9/L SGOT ≤ 2.5X upper limit of normal (ULN) SGPT ≤ 2.5X upper limit of normal (ULN) Alkaline phosphatase ≤4x ULN Prior treatment for high grade glioma Previous exposure to Ras pathway inhibitors Other concurrent active malignancy (with the exception of cervical carcinoma in situ or non melanoma carcinoma of the skin, superficial bladder tumor [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry) Serious medical or psychiatric illness that would, in the opinion of the investigator, interfere with the prescribed treatment, including but not limited to: Congestive heart failure > NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension within the last 12 months Any condition limiting the patient's judgment capacity History of HIV infection, chronic hepatitis C or B as well as clinically active infections (> grade 2 NCI-CTC version 3.0) History of organ allograft Renal dialysis Evidence or history of bleeding diathesis Major surgery within 4 weeks of start of study treatment, except for neurosurgical resection

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-85.0, Osteoarthritis Criteria:Major inclusión 1. Adults of either gender, ages 35-85, in general good health 2. Diagnosed with OA of the knee, K-L Grade 2-3 3. History of positive response to NSAID's or COX-2 inhibitors 4. Able and willing to discontinue other medicinal OA therapies for length of the study (subjects may continue low dose aspirin for cardioprotection) 5. Females of child bearing potential must use acceptable method of birth control Major Unwilling or unable to read and sign informed consent document 2. Pregnant and nursing women 3. History of severe cardiovascular disease including, but not limited to chronic angina, congestive heart failure, uncontrolled hypertension, acute myocardial infarction within past year 4. K-L grade 1 or 4 OA of the target knee 5. chronic bleeding disorder or present use of anticoagulants 6. History of upper G-I bleed in the past 5 years 7. Significant renal disease including nephrotic syndrome, proteinuria >1 gm/24 hrs or serum Creatinine >2.0 8. Any arthritic disease that is or has the potential to affect the knees during the course of the study 9. Any other condition that might confound evaluation of the target joint including, but not limited to, bursitis, tendonitis or internal derangement in or about the knee, gait disturbances (e.g. mechanical, neurological conditions or disorders of the back), fibromyalgia, polyneuropathies, etc

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Sciatica Radiculopathy Spinal Diseases Musculoskeletal Diseases Neuromuscular Diseases Intervertebral Disk Displacement Chief complaint of pain and/or paresthesia in the lumbar spine with a distribution of symptoms that has extended distal to the gluteal fold on at least one lower extremity within the past 24 hours based on the patient's self-report Oswestry disability score of at least 20% Age at least 18 years and less than 60 years At least one of the following signs of nerve root compression: 1. Positive ipsilateral or contralateral straight leg raise test (reproduction of leg symptoms with straight leg raise < 70 degrees) 2. Sensory deficit to pinprick on the ipsilateral lower extremity 3. Diminished strength of a myotome (hip flexion, knee extension, ankle dorsiflexion, great toe extension, or ankle eversion) of the ipsilateral lower extremity 4. Diminished lower extremity reflex (Quadriceps or Achilles) of the symptomatic lower extremity Red flags noted in the patient's general medical screening questionnaire (i.e., tumor, metabolic diseases, RA, osteoporosis, spinal compression fracture, prolonged history of steroid use, etc.) Evidence of central nervous system involvement, to symptoms of cauda equina syndrome (i.e., loss of bowel/bladder control or saddle region paresthesia) or the presence of pathological reflexes (i.e., positive Babinski) Patient reports the complete absence of low back and leg symptoms when seated Recent surgery (< 6 months) to the lumbar spine or buttocks, or any fusion surgery of the lumbar spine or pelvis Recent (< 2 weeks) epidural steroid injection for low back and/or leg pain Current pregnancy Inability to comply with the treatment schedule

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme Anaplastic Astrocytoma Male or female patients of greater or equal18 years of age Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) Patients with a histologically confirmed low-grade brain tumor who relapse with an enhancing tumor on MRI can be evaluated for toxicity only Patients must have at least one confirmed and evaluable tumor site. *A confirmed tumor site is one in which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study Patients must have a Karnofsky performance status greater or equal to 60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of greater or equal to three months Patients must be able to understand informed consent. Informed consent must be obtained at the time of patient screening Because of known concerns with Avastin and wound healing, all craniotomy patients are eligible for the treatment if they have had a craniotomy &gt; two weeks prior to IA therapy. Craniotomy after SIACI bevacizumab therapy should wait 4 weeks Pre-enrollment coagulation parameters (PT and PTT) must be less than or equal to1.5X the IUNL Patients must have adequate hematologic reserve with WBC greater than or equal to 2800/mm3, absolute neutrophils greater than or equal to1500/mm3 and platelets greater than or equal to 100,000/ mm3 Pre-enrollment chemistry parameters must show: bilirubin&lt;1.5X the institutional upper limit of normal (IUNL); AST or ALT&lt;2.5X IUNL and creatinine&lt;1.5X IUNL

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-85.0, Kidney Disease Individuals eligible to participate in this study must meet all of the following Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures Age ≥ 18 years and ≤ 85 years Willing and able to comply with all study procedures Patients with eGFR of 20 to 60 ml/min/173m2 by the abbreviated (4-variable) MDRD equation and a relatively stable clinical course Sitting systolic blood pressure ≥ 100 mmHg prior to study entry (to people at risk from hypotension from dietary salt reduction) Individuals who meet any of the following will not be eligible to participate in the study Recent acute illness (≤1 month). Minor ailments such as a recovered common cold or allergic rhinitis would not be considered as but would be left to the site PI's discretion Recent hospitalization (≤1 month) unless clearly for a minor elective procedure unlikely to interfere with BIA measurements. The final decision will be left to the site PI's discretion Any psychological condition (including alcoholism) that could interfere with the patient's ability to comply with the study protocol Subjects with baseline 24-hour urinary sodium excretion ≤100 mmol/day Amputation of a limb other than fingers or toes Pacemaker, defibrillator, implantable pump, artificial joint, pins, plates or other types of metal objects in the body (other than dental fillings) Coronary stents or metal suture material in the heart

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Thoracotomy Sternotomy Written informed consent Thoracic surgery including thoracotomy and sternotomy Thoracic epidural analgesia Contraindications to epidural anesthesia or refusal Preoperative residual urine volume > 100ml International Prostate Symptom Score (IPSS) > 7 Pregnancy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-120.0, Brain and Central Nervous System Tumors Neurotoxicity Histologically confirmed* supratentorial low-grade glioma, including 1 of the following Grade 2 astrocytoma Grade 2 oligodendroglioma Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma) NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time Paraffin-embedded tumor specimen available for submission for confirmation of pathological review and determination of 1p and 19q deletion status Patients must currently meet ≥ 1 of the following criteria* Uncontrolled symptoms, defined as any of the following Headaches associated with mass effect Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain and Central Nervous System Tumors Histologically confirmed malignant glioma, including any of the following subtypes Glioblastoma multiforme Gliosarcoma Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma not otherwise specified Must show unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast Candidate for surgery AND requires surgery Evaluable or measurable disease following resection of recurrent tumor is not required Not pregnant or nursing Negative pregnancy test No other medical issues (e.g., bleeding, infection, HIV, or serious medical or psychiatric illness) that would preclude study therapy Myocardial infarction within the past 6 months No other active cancer(s) except non-melanoma skin cancer or carcinoma in situ of the cervix, unless in complete remission and off of all therapy for that cancer for ≥ 3 years No hypersensitivity to bortezomib, boron, or mannitol More than 4 weeks since prior radiotherapy At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas) At least 3 weeks since prior investigational drugs At least 2 weeks since prior enzyme-inducing anticonvulsants

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, Glioblastoma Multiforme Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Mixed Oligoastrocytoma Patients with histologically proven malignant primary gliomas who have progressive disease after radiotherapy will be eligible for this protocol. These glioblastoma multiforme (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), and malignant glioma/astrocytoma NOS. Patients must have an magnetic resonance imaging (MRI)/computed tomography (CT) scan performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI/CT is required. The same type of scan, that is, MRI or CT must be used throughout the period of protocol treatment for tumor measurement. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: Patients will be eligible four weeks after surgery if they have recovered from the effects of surgery. Residual disease following resection of recurrent tumor is not mandated for into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, and within 14 days of registration, and on a steroid dosage that has been stable for at least 5 days. If the 96 hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days. Patients must have failed prior radiation therapy. All patients or their previously designated durable power of attorney (DPA) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must be greater than or equal to 18 years old, and must have a life expectancy greater than 8 weeks. Patients must have a Karnofsky performance status of greater than or equal to 60. Patients must be at least six weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, and 2 weeks from last vincristine administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents. Patients must have adequate bone marrow function (white blood cell (WBC) greater than or equal to 3,000/microL, absolute neutrophil count (ANC) greater than or equal to 1,500/mm(3), platelet count of greater than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase 2.5 less than or equal to upper limit of normal (ULN) and bilirubin less than or equal to 1.5 times ULN), and adequate renal function (creatinine less than or equal to 1.5 mg/dL and/or creatinine clearance greater than or equal to 60 cc/min) before starting therapy. Patients must also have serum potassium greater than or equal to 3.5 mg/dL, magnesium greater than or equal to 0.75 mmol/L and calcium levels within normal levels; supplementation is allowed. In cases where the serum calcium is below the normal range, 2 options would be available: 1) the calcium adjusted for albumin is to be obtained and substituted for the measured serum value. is to then be based on the adjusted for albumin values falling below the normal limit. 2) Determine the ionized calcium levels. is then to be based if these ionized calcium levels are out of normal range despite supplementation. These tests must be performed within 14 days prior to registration. level for hemoglobin may be reached by transfusion. Patients must either not be receiving steroids, or be on a stable dose of steroids for at least five days prior to registration. This study was designed to women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No to this study will be based on race. Minorities will actively be recruited to participate. Patients must not be pregnant or nursing, and all patients (both men and women) must be willing to practice birth control during and for 2 months after treatment with vandetanib and/or carboplatin. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test. In addition, WCBP patients must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner). A 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial entry with corrected QT interval (QTc) less than 480 msec. If a patient has a QT interval corrected for heart rate using Bazett's) QTcB interval > 480 ms on screening ECG, the screening ECG may be repeated twice [at least 24 hours apart] for a total of 3 ECGs. The average QTcB from the 3 screening ECGs must be less than or equal to 480 ms in order for the patient to be eligible for the study) Patients who, in the view of the treating physician, have significant active hepatic, renal, or psychiatric diseases are ineligible. Prior treatment with vandetanib. Prior treatment with platinum-based therapy. Patients known to have an allergic response to mannitol. Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease greater than or equal to 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia. History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology for Adverse Events (CTCAE) grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. QTc prolongation with other medications that required discontinuation of that medication. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age. Presence of left bundle branch block (LBBB.) QTc with Bazett's correction that is unmeasurable, or greater than or equal to 480 msec on screening ECG. (Note: If a subject has a QTc interval greater than or equal to 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be less than 480 msec in order for the subject to be eligible for the study. Patients who are receiving a drug that has a risk of QTc prolongation excluded if QTc is greater than or equal to 460 msec. Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes. Drugs listed in Appendix E, Table 2, that in the investigators opinion cannot be discontinued are allowed; however, must be monitored closely with additional ECGs and laboratory assessments of electrolytes to ensure the patients safety. Concomitant medications that are potent inducers (rifampicin, rifabutin, St. Johns Wort and Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs) of cytochrome P450 3A4 (CYP3A4) function. EIAEDs are allowed. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg) Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib or tolerate diarrhea. Women who are currently pregnant or breast feeding. Patients known to have a malignancy (other than their malignant glioma) that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except for non-melanoma skin cancer, carcinoma in situ in the cervix or ductal carcinoma in situ). Invasive procedures defined as follows Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy Anticipation of need for major surgical procedures during the course of the study Core biopsy within 7 days prior to Day 1 (D1) therapy Patients should not be on anti-platelet medications (aspirin, clopidogrel, ticlopidine, prasugel). Non-steroidal anti-inflammatory drugs should be used with caution if medically necessary. Restrictions Patients who are blood donors should not donate blood during the trial and for 3 months following their last dose of trial treatment Due to the experimental nature of vandetanib, all patients of childbearing potential must be one year post-menopausal, surgically sterile, or using an acceptable method of contraception (oral contraceptives, barrier methods in conjunction with spermicide, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) during and continued after the last dose of study medication. Contraceptive use will continue for at least two months, five half-lives, after the last dose on study medication

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain and Central Nervous System Tumors Patients with newly diagnosed high-grade gliomas Patients participating in NCCTG/Alliance or Mayo protocols Willing to provide mandatory blood and tissue samples for research purposes; note: 15 unstained slides may be submitted in place of a tissue block

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Herniated Disc Intervertebral Disc Displacement Signed Informed Consent Age:18 to 60 Weight: 60 to 80 Kg ASA Class: I,II Concordant physical and imaging findings in favor of symptomatic lumbar disk herniation Single level lumbar disk herniation unresponsive to medical treatment Previous consumption of Gabapentin or Amitriptyline Known allergy to investigated drugs Reluctant to sign informed consent Previous history of intolerance to narcotics Simultaneous lumbar diskectomy and a fusion technique Known renal failure Pregnancy Contraindications to Amitriptyline or Gabapentin prescription Unable to use PCA Habitual use of alcohol or opium

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-55.0, Musculoskeletal Pain Signed and dated informed consent prior to participation Subjects in good health as determined by the Investigator Age 18-55 Willing to abstain from any physical therapy, hard physical work, exercise or sauna during the study observation period (Screening to Final Visit) For females, subjects of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year) must be using appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectables, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner). Oral contraceptive medications are allowed in this study. Female subjects, who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) are also allowed for participation Participation in another clinical study within the last 30 days and during the study Subjects who are inmates of psychiatric wards, prisons, or other state institutions Investigator or any other team member involved directly or indirectly in the conduct of the clinical study Pregnancy or lactation Alcohol or drug abuse Malignancy within the past 2 years with the exception of in situ removal of basal cell carcinoma Skin lesions, dermatological diseases or tattoo in the treatment areas Known hypersensitivity or allergy (including photoallergy) to NSAID´s including celecoxib, sulfonamides and ingredients used in pharmaceutical products and cosmetics including galactose Varicosis, thrombophlebitis and other vascular disorders of the lower extremities Major traumatic lesions (e.g. fracture, tendon or muscle ruptures) of the musculo-skeletal system of the lower limbs

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, HIV Infection Liver Failure Evidence of Liver Transplantation Age ≥ 18 Documented HIV-1 infection, hepatitis B or C co-infection is allowed Plasma viral load at screening visit below 50 copies per mL for at least 6 months Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1 Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2 Abstinence from alcohol intake for at least 6 months (WHO norm) Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted) No ongoing class C opportunistic infection (1993 CDC classification) Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide *An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance" More than two virological failures during antiretroviral treatment Currently receiving treatment with an agent in development (apart from an authorization for temporary use) Plasma viral load at screening visit ≥ 50 copies per mL during at least the last 6 months Pregnant women, or women liable to become pregnant, breast-feeding women, no contraception, or refusal to use contraception All conditions (including but not limited to alcohol intake and drug use) liable to compromise, in the investigator's opinion, the safety of treatment and/or the patient's compliance with the protocol Patient not having any effective options for NRTI +/ enfuvirtide (defined in the criteria) Ongoing treatment with interferon-alpha or ribavirin for hepatitis C Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations anti-infective agents: rifampicin/rifampin

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.5-999.0, HIV Infection Rheumatic Disease Cancer Transplant Pediatrics medically recommended influenza A(H1N1) immunization signed informed consent failure or refusal to provide sufficient blood for antibody determination

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-59.0, First Episode Psychosis Aged 18-59 years and meet DSM-IV diagnostic for first episode of schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder NOS as assessed by using the Structured Clinical Interview for DSM-IV, research version Meeting DSM-IV for another axis I diagnosis, including substance abuse or dependence Needing another nonantipsychotic psychotropic medication at enrollment Having a serious or unstable medical illness Pregnant or lactating women or women without adequate contraception will be also excluded

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Metastatic Melanoma ENTRY Locally advanced or metastatic melanoma Measurable Histologically or cytologically confirmed Surgically incurable HLA-A2 positive and tumors that present HLA-A2.1/p53aa264-272 complexes PRIOR/CONCURRENT If prior Proleukin treatment, must have had clinical benefit No prior systemic cytotoxic chemotherapy for melanoma No concurrent radiotherapy, chemotherapy, or other immunotherapy More than 4 weeks since prior major radiotherapy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioma Patients Patients aged 18 or older with histological diagnosis of anaplastic astrocytoma (WHO grade III) or glioma (WHO grade IV) Assigned to bevacizumab treatment (monotherapy or adjunctive to chemotherapy) for therapeutic reasons by an oncologist Patients should be on a stable or decreasing dose of steroids Willingness and ability to comply with the protocol Patient should present with a KPS of >=70 Signed informed consent Previous anti-angiogenic drugs other than bevacizumab Allergy or hypersensitivity against bevacizumab Contraindications to bevacizumab according to the Summary of Product of Characteristics Unwillingness to comply with regular assessments of response and performance of study-related procedures Any condition considered relevant for proper performance of the study or risk to the patients, at the discretion of the investigator

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 45.0-80.0, Osteoarthritis Osteoarthritis of knee Appropriate candidate for chronic NSAID therapy due to moderate or severe pain on most days in the 28 days before screening for study Pregnant/Nursing women History of GI bleeding, perforation or obstruction A documented symptomatic GI ulcer during past 5 years Presence of GI ulcer or more than 2 erosions on screening endoscopy Allergy to naproxen (or naproxen intolerance), acetylsalicylic acid, or other NSAID drug

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Pulmonary Disease Patients preparing for lung transplant Diagnoses included are: Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis, Sarcoidosis, Cystic Fibrosis, or Bronchiectasis Primary Pulmonary Hypertension Multi-organ transplant patients Re-transplant patients Patients requiring intubation greater than or equal to 7 days prior to transplant Any orthopedic condition which will prevent from participation in a lower extremity strengthening program

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Anaplastic Astrocytoma Anaplastic Ependymoma Anaplastic Meningioma Anaplastic Oligodendroglioma Brain Stem Glioma Ependymoblastoma Giant Cell Glioblastoma Glioblastoma Gliosarcoma Grade III Meningioma Meningeal Hemangiopericytoma Mixed Glioma Pineal Gland Astrocytoma Brain Tumor Histological verification of grade III or IV MG at original diagnosis Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of radiation therapy Expression of IL13Ralpha2 by immunohistochemistry Karnofsky performance status (KPS) >= 60 Disease recurrence/progression in the cerebral hemisphere, which is in at least one area of enhancement amenable to biopsy after protocol enrollment in the following locations Adjacent or near previous resection cavity Distant from primary location; this includes tumor spread to contralateral hemisphere, corpus callosum, thalamus, basal ganglion, or subependymal locations Research participant has recovered from toxicity of prior therapies; an interval of at least 12 weeks must have elapsed since the completion of radiation therapy; at least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen; and at least 4 weeks since the completion of a non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment History of prior treatment with Temodar if no evidence of intolerance; documentation of intolerance to Temodar is not required Creatinine < 1.6 Survival expectation less than 4 weeks Pulmonary Requirement for supplemental oxygen use that is not expected to resolve within 2 weeks, Cardiac Uncontrolled cardiac arrhythmia, hypotension requiring pressor support, Renal Dialysis dependent, Neurologic refractory seizure disorder, clinically evident progressive encephalopathy Tumors with the following characteristics Large tumor recurrence causing significant symptoms from brain shift or mass effect, and thus not requiring "decompressive" craniotomy Tumors located primarily in the basal ganglion or thalamus Tumors with significant involvement of midbrain, cerebellum, pons and medulla will be excluded due to neurological risks associated with edema exacerbation from therapy

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Diffuse Astrocytoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Oligodendroglioma Recurrent Adult Brain Tumor Histologically proven malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) which is progressive or recurrent after radiation therapy +/ chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/ chemotherapy and are biopsied and found to have a high grade glioma are eligible Karnofsky performance status of >= 60% Patients both males and females with reproductive potential (i.e., premenopausal or menopausal for less than 1 year and not surgically sterilized) must practice at least 2 contraceptive measures throughout the study Patients must be registered and meet all the requirements of iPLEDGE in order to receive 13-cis-Retinoic Acid (CRA) Patients must provide verbal and written informed consent to participate in the study Patients must have a Mini Mental Status Exam score >= 15 Patients must have a 12-lead electrocardiogram (EKG) without evidence of any clinically significant abnormalities Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelets >= 100,000/mm^3 Aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN) (ULN = 50 U/L) Alanine aminotransferase (ALT) =< 2.5 ULN (ULN = 50 U/L) Total Bilirubin =< 1.5 mg/dL Alkaline phosphatase (Alk. Phos) =< 5X ULN (ULN = 125 U/dL) Estimated (Estim.) creatinine (Cr) Clearance > 50 ml/min Fasting total cholesterol < 300 mg/dL Fasting triglycerides < 250 mg/dL Two separate, laboratory pregnancy tests within 14 days of registration (for women of childbearing potential) Patients must have recovered from the toxicity of prior therapy; specifically, there must be at least a 3 month interval from the completion of the most recent course of radiation therapy, at least a 3 month interval from the implantation of Gliadel wafer(s), at least a 3 week interval from the completion of a non-nitrosourea-containing chemotherapy regimen, and at least a 6 week interval from the completion of a nitrosourea-containing chemo-regimen Pregnant or breast-feeding women Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction, severe psychiatric illness that would limit compliance with study requirements, or any other disorder that would be incompatible with the study therapy Any history of inflammatory bowel disease Any history of uncontrolled depression, any history of hospitalization for depression, or any history of suicidal thoughts or attempt(s) Patients receiving concurrent therapy for their tumor (with the exception of steroids) Must have at least a 10 day interval from last dose of vitamin A, tetracyclines, micro-dosed progesterone preparations, norethindrone/ethinyl estradiol, St. John's Wort, fish oil supplements, or phenytoin or other P450 enzyme inducing antiepileptic drugs Current smokers (Smoking >= 11 cigarettes per day), as smoking increases metabolism and decreases serum levels of erlotinib Participants may not have received prior EGFR inhibitors for any disease Patients with a history of allergic reactions to 13-cis-retinoic acid (CRA) or compounds of similar biologic or chemical composition to CRA Known allergy to proton pump inhibitors

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Cancer Glioblastoma Multiforme Patients with histologically proven glioblastoma multiforme, gliosarcoma or anaplastic glioma will be eligible for the Phase I component. Anaplastic gliomas anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic oligoastrocytoma (AOA), or malignant glioma not otherwise specified (NOS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made. Only patients with histologically proven supratentorial glioblastoma multiforme or gliosarcoma will be eligible for the Phase II component. 2. Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan and should have failed radiation therapy. Patients should have completed radiation therapy at least 3 months prior to entry into the study. The scan done prior to study entry documenting progression will be reviewed by the treating physician to document changes in tumor dimension to confirm recurrence. 3. (2. continued) Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have reasonable confirmation of true progressive disease rather than radiation necrosis as determined by the treating physician and neuro-radiologist; for example, through MRI, magnetic resonance (MR) spectroscopy, or PET scan of the brain. 4. For the Phase I component, any number of prior relapses is allowed, provided the patient fulfills all other particularly that of the functional status. For the phase II component, patients may have had up to 2 prior relapses 5. All patients must sign an informed consent indicating their awareness of the investigational nature of this study in keeping with the policies of this hospital. 6. The baseline on-study MRI should be performed within 14 days (+/ days) prior to registration and on a steroid dosage that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and the initiation of therapy (or at that time), a new baseline MRI is required. The same type of scan, i.e., MRI, must be used throughout the period of protocol treatment for tumor measurement. 7. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: a) They have recovered from the effects of surgery. b) Evaluable or measurable disease following resection of recurrent tumor is not mandated for into the study. c) To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively. 8. Patients must be 18 years old or older. 9. Patients must have a Karnofsky performance status (KPS) equal or greater than 60 10. Patients must have recovered from the toxic effects of prior therapy to grade 1 non hematological or </= grade 2 hematological toxicity (except deep vein thrombosis): 4 weeks from prior cytotoxic therapy or bevacizumab and/or at least two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, cis-retinoic acid, etc. (radiosensitizer does not count). 11. (10. continued) Patients who receive anticancer agents for non-therapeutic purposes unrelated to this study (such as presurgically for obtaining pharmacology data for the agent) will be eligible to enter the study provided they have recovered from the toxic effects of the agent if any. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. 12. Patients must have adequate bone marrow function (ANC>/= 1,500/mm^3 and platelet count of >/= 100,000/mm^3), adequate liver function (SGPT </= 3 times normal and alkaline phosphatase </= 2 times normal, bilirubin </= 1.5 mg/dl), adequate renal function (BUN and creatinine </= 1.5 times institutional normal) prior to registration. 13. Women of childbearing potential on treatment must not be pregnant, must not be breast-feeding and must practice adequate contraception. Male patients on treatment with vorinostat must agree to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix or bladder), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible. 2. Patients must not have: a) active infection b) disease that will obscure toxicity or dangerously alter drug metabolism, especially liver disease including cirrhosis or hepatic dysfunction c) serious intercurrent medical illness 3. Patients who are currently on active treatment for AIDS or hepatitis will be excluded due to the potential for adverse interaction with ongoing treatment agents and for unknown toxicity. 4. Patients receiving valproic acid (VPA), an anticonvulsant drug with histone deacetylase (HDAC) inhibitor properties, will be excluded, unless they are switched to an alternative agent prior to treatment initiation. A 5 day wash out period is required. 5. Prior treatment with EGFR inhibitors or temozolomide on a standard day 1-5 dosing and low dose daily dosing as part of chemoradiation therapy is allowed because the trial is based on the hypothesis that the combination of agents used will be synergistic in their effects, and that HDAC inhibition will potentially overcome resistance to EGFR inhibitors and temozolomide. However, prior treatment with dose dense regimens of temozolomide (7 days on/ 7 days off, 21 days/28 days or continuous low dose daily dosing not with chemoradiation) and HDAC inhibitors other than valproic acid (such as depsipeptide, LBH-589 or vorinostat) are not permitted. 6. Patients with a known allergy to any component of vorinostat, or a known allergy to Temozolomide or erlotinib will be excluded. 7. Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study. Inability to comply with protocol or study procedures (for example, an inability to swallow tablets) will be an criteria. 8. This study was designed to women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. 9. No to this study will be based on race. The malignant glioma patient population treated at MD Anderson Cancer Center (MDACC) over the past year is as follows: American Indian or Alaskan Native Asian or Pacific Islander <2%; Black, not of Hispanic Origin ; Hispanic ; White, not of Hispanic Origin - 88%; Other or Unknown ; Total-100%

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Breast Cancer Fatigue Age > 18 years 2. Pathologic diagnosis of stage 0-III breast cancer (any histologic subtype) in either breast or both breasts 3. Previous resection of tumor, either by mastectomy or partial mastectomy, ±sentinel lymph node biopsy, ±axillary lymph node dissection 4. A likelihood of having radiation therapy or chemotherapy following surgery as determined by the on-site principal investigator (PI) or co-investigator 5. Signed informed consent which has been reviewed and approved by the Institutional Review Board and no condition that impairs the ability to provide informed consent (e.g. uncontrolled psychiatric illness) for the radiation therapy (RT) alone group will 1. Planned 3-D conformal radiation therapy to the whole breast (2 tangential fields, unilateral or bilateral) via standard or Canadian Fractionation, +/ regional nodal irradiation. 2. No planned chemotherapy for this tumor for the RT + chemotherapy (CT) group will 1. Planned 3-D conformal radiation therapy to the whole breast (2 tangential fields, unilateral or bilateral) via standard or Canadian fractionation (photons followed by a photon, electron, or mixed photon/electron boost), +/ regional nodal irradiation. 2. Planned adjuvant chemotherapy (any regimen except for biologic therapy alone) Continuous/chronic treatment with opiate/opioid analgesics for 3-6 months prior to enrollment. In addition, patients receiving radiation therapy alone who have taken opiate analgesics from their surgery within 72 hours of the post-surgery/pre-radiation therapy blood draw (at 1-6 weeks prior to the start of radiation therapy) will be removed from the study. Patients receiving chemotherapy and radiation therapy who have taken opiate analgesics from their surgery within 72 hours of the blood draw prior to cycle 1 of chemotherapy will be removed from the study. 2. Prior radiation therapy to the chest or brain 3. Patients diagnosed with Stage IV breast cancer 4. History of illegal drug use within 6 months prior to enrollment 5. At point of enrollment, diagnosis of major depression, bipolar disorder, seasonal affective disorder, or anxiety disorder for which the patient is currently taking any of the following medications: selective serotonin reuptake inhibitors (SSRIs), Tricyclic antidepressants, monoamine oxidase inhibitors, lithium, benzodiazepines, barbiturates, drugs acting on the 5-HT receptors. Patients meeting these may still enroll in the study if they are on a chronic, stable, low-dose regimen for at least 3 months prior to enrollment, as determined by the on-site PIs and co-investigating physicians. Patients having to begin on a regimen of any of these medications while on the study may continue on the study. 6. Anemia of any etiology at initial visit (Hct <33%) and the following baseline fatigue scores on the Fatigue Symptom Inventory (FSI): Average score for question #s 1-4 > 5; and/or Average score for question #s 5-11 > 5. Patients with Hct<33% but who have no baseline fatigue (as indicated by baseline scores on the FSI as follows: average score for question #s 1-4 < 5 and average scores for question #s 5-11 < 5) are eligible to participate. 7. Endocrine disorders that can cause fatigue: Addison's disease, uncorrected hypothyroidism (patients taking thyroid replacement therapy for at least 3 months prior to enrollment patients are eligible), central endocrine deficiency, polyglandular autoimmune failure. 8. Patients with thyroid disease (hypothyroidism or hyperthyroidism) that was diagnosed within 3 months of cancer diagnosis or patients with previously stable thyroid disease who have experienced symptoms or have had to change their medication doses within 3 months of cancer diagnosis. Patients with stable disease who have no had to change medication doses within 3 months of cancer diagnosis. Patients with stable disease who have not had to change medication doses within 3 months of cancer diagnosis may enroll as long as baseline fatigue scores do not meet for exclusion. Patients enrolled in the study who have to alter doses of thyroid medications or who are newly diagnosed with thyroid disease while on the study will be removed from the study, and will not count towards our total patient accrual. 9. Uncontrolled autoimmune diseases that can cause fatigue, including fibromyalgia and fatigue syndromes. If these are controlled, enrollment or maintenance of the patient on the protocol may continue at the discretion of the enrolling principal investigator. 10. Sleep disorder diagnosed within 3 months of enrollment and the following baseline fatigue scores on the FSI: Average score for question #s 1-4 > 5; and/or average score for question #s 5-11 > 5. Patients diagnosed with a sleep disorder within 3 months of enrollment and with FSI scores < 5 on question #s 1-4 and #s 5-11 are eligible. 11. Activity-limiting heart or lung disease 12. Renal failure (BUN and creatinine should be within the normal range for the prior 6 months) 13. Baseline fatigue as indicated by the following baseline scores on the FSI: Average score for question #s 1-4 > 5; and/or Average score for question #s 5-11 > 5. 14. Patients receiving chemotherapy or radiation therapy at any site other than Massachusetts General Hospital 15. Hepatitis or chronic liver disease (albumin <3 g/dL or >6 g/dL; ALT >60 U/L or < 5 U/L, AST > 40 U/L or <5 U/L) 16. Untreated chronic infection (e.g. tuberculosis, osteomyelitis, abscess). Patients being treated for these may be enrolled in, or continue on the protocol at the discretion of the principal investigators

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-999.0, Acoustic Schwannoma Adult Anaplastic (Malignant) Meningioma Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Brain Stem Glioma Adult Choroid Plexus Neoplasm Adult Craniopharyngioma Adult Diffuse Astrocytoma Adult Ependymoblastoma Adult Ependymoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Grade I Meningioma Adult Grade II Meningioma Adult Medulloblastoma Adult Mixed Glioma Adult Myxopapillary Ependymoma Adult Oligodendroglioma Adult Papillary Meningioma Adult Pilocytic Astrocytoma Adult Pineal Gland Astrocytoma Adult Pineoblastoma Adult Pineocytoma Adult Primary Melanocytic Lesion of Meninges Adult Subependymal Giant Cell Astrocytoma Adult Subependymoma Adult Supratentorial Primitive Neuroectodermal Tumor Malignant Adult Intracranial Hemangiopericytoma Patients must have newly diagnosed glioblastoma, anaplastic astrocytoma, gliosarcoma or other malignant gliomas with the exception of pure anaplastic oligodendroglioma; note: patients with presumed malignant glioma based on radiographic assessment may be enrolled onto Arm A of the study without histological confirmation provided they meet the following additional The MRI of the brain shows typical findings of a malignant glioma or glioblastoma (single ring-enhancing mass with necrotic portions) To brain abscess, diffusion-weighted MRI must show absence of restricted diffusion corresponding to the necrotic center of the lesion To confirm the diagnosis of neoplastic disease, MR perfusion must show that the lesion has increased perfusion To pilocytic astrocytoma, the patient's age must be over 25 To brain metastasis, a computed tomography (CT) of the chest, abdomen and pelvis must demonstrate absence of other malignancy The principal investigator must review MRI and CT findings and agree with diagnosis of presumed malignant glioma Note: If after the on-protocol surgery the patient is found not to meet histological described (diagnosis of glioblastoma, anaplastic astrocytoma, gliosarcoma or other malignant gliomas with the exception of pure anaplastic oligodendroglioma), the patient will be removed from the study and replaced ARM A ONLY: Patients must have an indication for additional debulking surgery as part of their initial treatment Life expectancy of greater than 2 months Prior chemotherapy, radiotherapy, biological or experimental therapy for glioma Prior history of radiotherapy to the brain, head or neck Patients may not be receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or other agents used in the study Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible Preclinical studies indicate that RO4929097 is a substrate of CYP3A4 and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; if such patients cannot be switched to alternative medications, they will be ineligible to participate in this study Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow tablets Patients with known history of hepatitis B or C, or who have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible; (hepatitis B and C serology should be obtained as part of pre-treatment evaluation but are not required for eligibility) Patients with uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, and hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, history of torsades de pointes or other significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Adult Alveolar Soft Part Sarcoma Adult Angiosarcoma Adult Desmoplastic Small Round Cell Tumor Adult Epithelioid Hemangioendothelioma Adult Epithelioid Sarcoma Adult Extraskeletal Myxoid Chondrosarcoma Adult Extraskeletal Osteosarcoma Adult Fibrosarcoma Adult Leiomyosarcoma Adult Liposarcoma Adult Malignant Mesenchymoma Adult Malignant Peripheral Nerve Sheath Tumor Adult Rhabdomyosarcoma Adult Synovial Sarcoma Adult Unclassified Pleomorphic Sarcoma Chondrosarcoma Clear Cell Sarcoma of the Kidney Conjunctival Kaposi Sarcoma Dermatofibrosarcoma Protuberans Gastrointestinal Stromal Tumor Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Metastatic Osteosarcoma Ovarian Sarcoma Recurrent Adult Soft Tissue Sarcoma Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Kaposi Sarcoma Recurrent Osteosarcoma Recurrent Uterine Corpus Sarcoma Small Intestine Leiomyosarcoma Stage III Adult Soft Tissue Sarcoma Stage III Uterine Sarcoma Stage IV Adult Soft Tissue Sarcoma Stage IV Uterine Sarcoma Unclassified Pleomorphic Sarcoma of Bone Patients must have histologically or cytologically confirmed sarcoma All Patients must have measurable disease as defined by 1.1 Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) There is a minimum of 1 prior therapy; however, there are no minimum systemic therapy requirements for well differentiated or de-differentiated liposarcoma, clear cell sarcoma, chondrosarcoma, alveolar soft part sarcoma and chordomas which have no effective therapies; for Phase Ib, there are no maximum limits to number of prior therapies; for Phase II, there is a maximum of 5 prior chemotherapy regimens including tyrosine kinase inhibitors (TKI); the last dose of systemic therapy (including TKI) must have been given at least 2 weeks prior to initiation of therapy; patients receiving nitrosourea (such as BCNU) or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy; patients receiving bevacizumab must wait at least 4 weeks; patients receiving experimental immunotherapy or antibody based therapies must wait a minimum of 4 weeks or 4 half-lives, whichever is longer; this should be discussed with the principal investigator before registration; tumor biopsies should be performed only after meeting these requirements; patients should recover to less than Common Terminology for Adverse Events (CTCAE) grade 2 toxicities related to previous therapies to be eligible Patients with metastatic or locally advanced (inoperable) gastrointestinal stromal tumor (GIST) must have progressed on imatinib and sunitinib or be intolerant to both drugs; the last dose of tyrosine kinase inhibitors imatinib or sunitinib should be given at least 2 weeks prior to initiation of therapy Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids are eligible for study Patients must not have current evidence of another malignancy except non-melanoma skin cancer and superficial bladder cancer Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Hemoglobin >= 9 g/dl Patients may not receive other investigational agents within 2 weeks of enrollment in this study; patients treated with bevacizumab should be off therapy for 4 weeks; other experimental or immuno therapies should wait for 4 half-lives or 4 weeks, whichever is longer; prior exposure to Notch or Hedgehog inhibitors is not allowed; patients who have not recovered to less than CTCAE grade 2 from prior therapies are ineligible History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or RO4929097 used in the study Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible; patients on warfarin may be considered for enrollment after cessation of warfarin and appropriate transition to alternate anti-coagulation agents Preclinical studies indicate that RO4929097 is a substrate of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; the following medications with strong potential for interaction are not allowed: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone Caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8), CYP2C9, and CYP2C19 and have narrow therapeutic windows; caution should be exercised when dosing GDC-0449 concurrently with inhibitors of CYP3A4 Patients must be able to swallow pills; patients with malabsorption syndrome or other condition that would interfere with intestinal absorption Patients with clinically active liver disease, including active viral or other hepatitis or cirrhosis, are ineligible Patients with uncontrolled electrolyte abnormalities including hypophosphatemia, hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia or defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, a history of torsades de pointes or other significant cardiac arrhythmias that require antiarrhythmics or other medications known to prolong corrected QT interval (QTc); psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449 and/or RO4929097

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma at least 18 years of age for intratumoral cohorts, supratentorial HGG (WHO grade III or IV) technically unresectable HGG initial definitive therapy such as surgery with or without adjuvant radiation subject elected not to undergo treatment with Gliadel wafer if receiving corticosteroids, dose is stable or decreasing for past 7 days KPS: at least 70 absolute neutrophil count > 1500/mm^3 absolute lymphocyte count > 500/mm^3 platelet count > 100,000/mm^3 cytotoxic therapy within the past 4 weeks (6 weeks for BCNU/CCNU) more than 2 recurrences including present recurrence Gliadel wafer or wafers implanted within the past 8 weeks taking more than 8 mg of dexamethasone per day for intratumoral cohorts, injection of tumor would require violation of ventricular system any infection requiring antibiotic, anticoagulant, or antiplatelet agents within the past 4 weeks for intratumoral cohort, bleeding diathesis or use of anticoagulants/antiplatelet agents that cannot be stopped allergy or intolerance to 5-FC HIV positive g.i. condition that would prevent ingestion or absorption of 5-FC

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme Anaplastic Astrocytoma for Male or female patients of ≥18 years of age Patients with a documented histologic diagnosis of newly diagnosed or glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA) Patients must have at least one confirmed and evaluable tumor site.∗ *A confirmed tumor site is one in which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gad-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study Patients must have a Karnofsky performance status ≥60% (or the equivalent ECOG level of 0-2) and an expected survival of ≥ three months No other chemotherapy for two weeks prior to treatment under this research protocol Patients must have adequate hematologic reserve with WBC≥3000mm3, absolute neutrophils ≥1500mm3 and platelets ≥100,000 mm3. Patients who are on Coumadin must have a platelet count of ≥150,000 mm3 Pre-enrollment chemistry parameters must show: bilirubin<1.5X the institutional upper limit of normal (IUNL); AST or ALT<2.5X IUNL and creatinine<1.5X IUNL Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5X the IUNL Concomitant Medications Women who are pregnant or lactating Subjects who decline birth control. Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor Histologically confirmed malignant glioma (phase I) Glioblastoma Anaplastic astrocytoma Anaplastic oligodendroglioma Mixed anaplastic oligoastrocytoma Histologically confirmed glioblastoma following radiotherapy and temozolomide (phase II) Progressive or recurrent disease after conformal external-beam radiation therapy and concurrent temozolomide, followed by ≥ 1 adjuvant course of temozolomide Measurable disease by MRI within the past 2 weeks Tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of malignant glioma completed and signed by a pathologist Karnofsky performance status 60-100% No serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive the treatment outline in this protocol with reasonable safety No history of allergic reactions attributed to compounds of similar chemical or biological composition to gamma-secretase inhibitor RO4929097 or bevacizumab Must be able to swallow capsules No malabsorption syndrome or other condition that would interfere with intestinal absorption No baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) Not history of being serologically positive for hepatitis A, B, or C No history of cirrhosis No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia despite adequate electrolyte supplementation No uncontrolled intercurrent illness including, but not limited to, any of the following Ongoing or active infection

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 7.0-90.0, Hip Dysplasia All patients with radiographic and clinical diagnosis of DDH will be included Other forms of arthritis osteoarthritis inflammatory arthropathies vascular necrosis

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Malignant Glioma Female or male, adult patients of 18 to 70 years of age at time of diagnosis that qualify for standard treatment including surgery and radiotherapy. 2. Histologically confirmed diagnosis of 1 of the following malignant gliomas: Anaplastic astrocytoma Glioblastoma multiforme Oligodendroglioma Oligoastrocytoma 3. Newly diagnosed or recurrent disease 4. Patients must have had surgical resection at UCLA for the collection of their tumor. Total, subtotal, or partial resection of more then 70% of tumor mass defined by MRI. 5. After surgery, a pathological diagnosis of malignant glioma (WHO Grade III or IV) will need to be established. 6. Supratentorial tumour localisation. 7. Karnofsky performance status 60-100% 8. Life expectancy ≥ 12 weeks 9. Written informed consent of patient and/or legal guardian. 10. Must be off of steroid at least two weeks prior to vaccination 11. Hematologic and metabolic panel results will be within the parameters of the protocol. 12. Negative pregnancy test 13. Fertile patients must use effective contraception 14. Hepatitis B negative 15. Hepatitis C negative 16. HIV negative 17. Syphilis serology negative 18. Patient must have no prior sensitivity to the components of the dendritic cell vaccine Anti-neoplastic chemotherapy or radiotherapy during 4 weeks before entering the study, 2. Presence of acute infection 3. Inability to obtain informed consent because of psychiatric or complicating medical problems. 4. Unstable or severe intercurrent medical or psychiatric conditions as determined by the Investigator. 5. Subjects with organ allografts. 6. Contraindication to MRI 7. Known history of autoimmune disorder 8. Subjects who have an uncontrolled systemic malignancy that is not in remission. 9. Pregnancy or breast-feeding. 10. Positive for hepatitis B, C, HIV, syphilis 11. Patients unwilling to perform a save method of birth control

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Metastatic Epidural Spinal Cord Compression Greater than or equal to 18 years old 2. Radiographically documented metastatic epidural compression on spine Magnetic resonance imaging (MRI) within 4 weeks of registration, defined radiographically, ranging from minimal canal compromise and thecal indentation to actual displacement of the spinal cord. 3. Maximum of 3 contiguous vertebral levels involved with metastasis in the spine to be irradiated in a single session 4. Signed Informed consent for irradiation 5. Diagnosis of cancer including but not limited to non-small cell lung cancer, breast, prostate, renal cell, melanoma, gastrointestinal, sarcoma, thyroid, head and neck primary, and unknown primary tumors 6. Motor Strength >/= 4 out of 5 in extremity or extremities affected by the level of the spinal cord compression 7. Karnofsky performance status (KPS) >/= 40 8. Patients deemed to be inoperable due to patient refusal, by neurosurgical evaluation, or for any reason 9. 1 prior course of spine radiotherapy to the current region of interest Prior irradiation of the site to be treated </= 3 months prior to registration 2. Inability to tolerate lying flat on treatment table for greater than 30 minutes. 3. Patients unable to undergo MRI of the spine 4. Patients who have previously received maximum cord tolerance of 45 Gy in 5 weeks conventional fractionation or similar biologically effective dose (BED) to the area of the spine to be treated. Below are the normalized BED at 2 Gy per fraction with alpha/beta=2 for spinal cord in commonly used fractionation schemes in previously irradiated patients. Conventional Radiotherapy (Normalized Biologically Effective Dose) 20 Gy in 5 fractions(30 Gy 2/2), 30 Gy in 10 fractions(37.5 Gy 2/2), 37.5 Gy in 15 fractions(42 Gy 2/2), 40 Gy in 20 fractions(40 Gy 2/2), 45 Gy in 25 fractions(43 Gy 2/2), 50 Gy in 25 fractions(50 Gy 2/2) following equation: nBED is calculated by dividing BED by (1 + d/a/b), where d is 2 Gy and for spinal cord late effect a/b is 2, and we describe the units as Gy 2/2 (i.e., Gy 2/2 = 2-Gy equivalent with a/b = 2) 5. Patients who are pregnant. 6. Patients who have cord compression from bone components or configuration

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Cord Injuries Brown Sequard Central Cord Syndrome Adults at least 18 years of age At least 12 months post-incomplete spinal cord injury (I-SCI), including but not limited to the following syndromes: Brown Sequard and Central Cord Syndromes Upper motor neuron lesion (with upper motor neuron signs (i.e. presence of clonus, spasms, and/or hyperreflexia)) A diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic pathology Resting oxygen saturation (SpO2) levels of 95-99% Individuals who ambulate independently, with an assistive device, or who can walk when provided manual assistance Persons using anti-spasticity medication must maintain stable medication dosage during the study Able to give informed consent Medical approval by individual's physician Current participation in a rehabilitation program/research protocol that could interfere or influence the outcome measures of the current study History of congenital SCI (e.g. myelomeningocele, intraspinal neoplasm, Frederich's ataxia) or other degenerative spinal disorders (e.g. spinocerebellar degeneration, syringomyelia) that may complicate the protocol Inappropriate or unsafe fit of the harness due to the participant's body size and/or joint contractures or severe spasticity that would prohibit the safe provision of either training modality Severe spasticity that would prohibit the safe provision of training Pregnancy all women of childbearing age will be required to undergo pregnancy testing prior to enrollment Unstable medical condition that could interfere with safety during participation in study (i.e. symptomatic cardiopulmonary complication, osteoporosis, contractures or other significant medical complications that would prohibit or interfere with testing of walking function and training or alter compliance with a training protocol)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Bronchiectasis Male/Female 18 years or older with non-CF bronchiectasis Chronic sputum production on most days Positive sputum culture for gram-negative organisms Must have met lung function requirements History of CF Hospitalized within 14 days prior to joining the study Previous exposure to AZLI Pregnant, breastfeeding, or unwilling to follow contraceptive measures for the study Must have met liver and kidney function requirements Continuous oxygen use of greater than 2 liters per minute (supplemental oxygen with activity and at night was allowed) Treatment for nontuberculous mycobacteria infection or active mycobacterium tuberculosis infection within 1 year of enrollment Other serious medical conditions

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Bronchiectasis Male/Female 18 years or older with non-CF bronchiectasis Chronic sputum production on most days Positive sputum culture for gram-negative organisms Must have met lung function requirements History of CF Hospitalized within 14 days prior to joining the study Previous exposure to AZLI Pregnant, breastfeeding, or unwilling to follow contraceptive measures for the study Must have met liver and kidney function requirements Continuous oxygen use of greater than 2 liters per minute (supplemental oxygen with activity and at night was allowed) Treatment for nontuberculous mycobacteria infection or active mycobacterium tuberculosis infection within 1 year of enrollment Other serious medical conditions

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Metastases Vertebral Metastases Benign Spinal Tumors Chordoma Meningioma Schwannoma Neurofibroma Paragangliomas Arteriovenous Malformations Patient age >= 18 years performance status of 0-3 Vertebral and/or paraspinal metastases, with or without prior surgery and/or fractionated radiotherapy Benign extradural spine tumors such as chordomas, meningiomas, schwannomas, neurofibromas, paragangliomas, and arteriovenous malformations (AVMs) Established histologic diagnosis of a benign or malignant tumor of the spine Arteriovenous malformation of the spine identified radiographically (no biopsy) Well-defined lesion involving no more than 2 adjacent vertebral levels or spinal segment Minimal spinal canal compromise that is not rapidly progressive. Ideally, the tumor should not be within 5 mm of the spinal cord If chemotherapy is planned, ideally it should not have been given within 30 days of starting radiation and should not resume until at least 2 weeks after completing radiation. In addition, it is not recommended to perform SBRT when targeted anti-angiogenesis therapy is planned within 2 months of the procedure Signed study-specific consent form Lesion involving > 3 adjacent vertebral levels Overt spinal instability Neurologic deficit due to bony fragments/bony compression of neural structures Prior radiotherapy at the involved level(s) within 3 months of radiosurgery, more than one prior course of radiotherapy at the involved level(s), or more than 45 Gy previous radiation exposure at the involved level(s) Rapidly progressive spinal cord compromise or neurological deficit Paralysis, or otherwise compromised motor function due to radiographically confirmed cord compression Patient unable to undergo an MRI Pregnant or lactating women, due to potential exposure of the fetus to RT and unknown effects of RT on lactating females Patients with psychiatric or addictive disorder that would preclude obtaining informed consent

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Breast Cancer Lung Cancer Dyspepsia Patients with newly diagnosed cancer (lung and breast cancer) Patients currently free of active disease History of cerebral edema, primary and secondary brain neoplasm with signs and symptoms of raised intracranial pressure and/or brain metastases Signs of marked hepatic or renal dysfunction, cardiac failure Signs of dyspepsia, peptic ulcer, gastric surgery or prior diagnosis of other cancer Administration of drugs interfering with GI motility (i.e. antisecretory, prokinetic, or antibiotic drugs) as well as the exposition to radiotherapy, four weeks prior to the examination Referred episode of nausea of any severity within 24 h prior to antiemetic therapy, if they had experienced vomiting in the previous 24 h Pregnancy or lactating Concomitant administration of agents known to have significant antiemetic activity, including benzodiazepines and other corticosteroids

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme Anaplastic Astrocytoma years of age or older Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA) Circumscribed tumor recurrence with less than 3.5 cm greatest diameter Patients with histologically confirmed low-grade brain tumor relapse with an enhancing tumor on MRI will be evaluated for toxicity only Patients must have at least one confirmed and evaluable tumor site Patients must have a Karnofsky performance status 70% (or the equivalent ECOG level of 0-2) Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period Women who are pregnant or lactating Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring Low GFR or history of hepatorenal syndrome

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Cancer MALIGNANT GLIOMA Glioblastoma Anaplastic Astrocytoma (AA) Anaplastic Oligodendroglioma (AO) Anaplastic Oligo-astrocytoma (AOA) Anaplastic Mixed Gliomas Malignant Glioma NOS Patients must have Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma, Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligo-astrocytoma (AOA) also called anaplastic mixed gliomas, Malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made. OR Histologically confirmed low grade (WHO grade II) gliomas (such as low grade astrocytoma, low grade oligodendroglioma, low grade oligo-astrocytoma (mixed gliomas), or low grade glioma NOS) IF there is radiographic evidence by MRI of malignant transformation but histologic confirmation of high grade (malignant) transformation would not be otherwise undertaken for routine clinical care. of patients in this group will allow increased accrual rapidity by enrolling patients who are otherwise ineligible for almost all malignant glioma trials yet whom are treated presumptively for malignant glioma. The primary aim of the phase I study is not determination of efficacy. Therefore, of such patients will not affect efficacy analyses. Participating site confirmation is adequate Able to undergo brain MRI scans MRI scan with gadolinium contrast showing geographically-circumscribed tumor ≤40 cc incorporating both enhancing and non-enhancing volume. This is calculated by the product of maximum measurements in 3 dimensions divided by 2. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. (The MRI must be performed on a steroid dosage that has been stable or decreasing for at least 5 days. Patients on no steroids are eligible. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required) Prior treatment with approximately 60 Gy of radiotherapy Patients must have recovered from the toxic effects of prior therapy including but not limited to An interval of ≥ 4 weeks (28 days) from prior cytotoxic therapy except 6 weeks from nitrosoureas An interval of ≥ 1 week (7 days) from any non-cytotoxic agents An interval of ≥ 3 months from the completion of radiation therapy Prior treatment with radiosurgery Prior disease progression/recurrence during or immediately following treatment with bevacizumab. Any question should be directed to the PI Multicentric glioma Other malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) for which there has been treatment within the last 3 years Serious medical or psychiatric illness that would in the opinion of the investigator interferes with the prescribed treatment Pregnant or breast feeding women Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) Any prior history of hypertensive crisis or hypertensive encephalopathy Grade 2 or greater congestive heart failure History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to Day 1

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Tumor Glioblastoma Anaplastic Glioma General 1. Patients with histologically proven recurrent intracranial malignant glioma will be eligible for the phase I/II component of this protocol. Malignant glioma includes glioblastoma (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made. 2. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information at all sites except the NIH. 3. Patients must be greater than or equal to 18 years old. 4. Patients must have a Karnofsky performance status of greater than or equal to 60. 5. No more than 2 prior chemotherapies and 1 relapse. Prior bevacizumab therapy is allowed. -Patients must have recovered from the toxic effects of prior therapy: >3 weeks for biologic therapies or non-cytotoxic therapies, >4 weeks for cytotoxic therapies, and >6 weeks for nitrosoureas. Any questions related to the definition of non cytotoxic agents should be directed to the Study Chair. NOTE: 13 cis-retinoic acid (Accutane) as biologic therapy has a washout period of 14 days. 6. Patients must have adequate bone marrow function (WBC >= 3.0 x 10^9/L, ANC >= 1.5 X 10^9/L, platelet count of >=100 x 10^9/L, and hemoglobin >= 10 gm/dL), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.7mg/dL or creatinine clearance greater than or equal to 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. level for hemoglobin may be reached by transfusion. 7. Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. Measurable disease is NOT required. Note: MRI is the preferable imaging method; CT scan may be used in cases where an MRI cannot be obtained. 8. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply They have recovered from the effects of surgery and be > 3 weeks from surgery Residual disease following resection of recurrent malignant glioma is not mandated for into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days. 9. Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 12 weeks from the completion of radiation therapy to registration; except if patients underwent surgery within 12 weeks and pathology is consistent with recurrent tumor. 10. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical/pathological documentation of disease. 11. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to taking the first dose of study medications. 12. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable. Phase I The following modifications to the general apply to Phase I patients only. -Patients may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e. surgery and radiation+/ chemo if that was used as initial therapy). Phase II Phase II patients must meet the following in addition to the General described above Patients may have had treatment for no more than 1 prior relapse (i.e. failed 2 lines of treatment-initial therapy and therapy for first relapse) at 2nd relapse, treatment per BTTC09-01 is an option. Relapse is defined as progression following initial therapy (i.e. radiation+/ chemo if that was used as initial therapy). The intent therefore is that patients had no more than 2 prior therapies (initial and treatment for 1 relapse). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse. For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse Patients must not have received prior therapy with sorafenib, everolimus, or related drugs such as tyrosine kinase inhibitors, VEGF inhibitors (except bevacizumab), or mTOR inhibitors General Patients has any significant medical illnesses that in the investigator s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient s ability to tolerate this therapy 2. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible. 3. Patients has an active infection or serious intercurrent medical illness. 4. Patients has any disease that will obscure toxicity or dangerously alter drug metabolism. 5. Patients must not be on enzyme inducing anti-convulsants. If patients were previously on EIAEDs and these have been discontinued, patients must have been off the agent for at least 2 weeks prior to first study drug administration. For patients who need to start an AED or the AED needs to be changed, it is strongly recommended that all efforts should be made to use a non-EIAED. 6. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Symptomatic congestive heart failure of New York heart Association Class III or IV unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug or any other clinically significant cardiac disease severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN, active (acute or chronic) or uncontrolled severe infections, liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. 7. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. 8. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management. 9. Known human immunodeficiency virus (HIV) infection or chronic or acute Hepatitis B or C. Note: Patients who have a history of HBV and HCB infection are eligible, however, they must receive prophylactic antiviral therapy for 1-2 weeks prior to receiving study drug 10. Thrombolic or embolic events (except DVT or pulmonary embolus) such as a Cerebrovascular accident including transient ischemic attacks within the past 6 months. 11. Pulmonary hemorrhage/bleeding event greater than or equal to CTCAE Grade 2 within 4 weeks of first dose of study drug. 12. Any other hemorrhage/bleeding event greater than or equal to CTCAE Grade 3 within 4 weeks of first dose of study drug. 13. Serious non-healing wound, non-healing ulcer, or bone fracture. 14. Evidence or history of bleeding diathesis or coagulopathy 15. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug. 16. Use of St. John s Wort, orrifampin (rifampicin), or other strong CYP34A inducers. Dexamethasone is okay as long as the dose is 16 mg /day or less. Note: Patients who are on the above referenced medications may be considered eligible with a washout period of 14 days. Contact the coordinating center to discuss patients with the above aforementioned agents before patient registration. 17. Known or suspected allergy to sorafenib, everolimus, or any agent given in the course of this trial. 18. Any condition that impairs patient s ability to swallow whole pills. 19. Any malabsorption problem. 20. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. 21. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Barrier contraceptives must be used throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus and sorafenib). 22. Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus). 23. Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients. 24. History of noncompliance to medical regimens. 25. Patients unwilling to or unable to comply with the protocol. 26. Patients on total daily dose of dexamethasone greater than 16 mg

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 2.0-999.0, Aplastic Anemia Short age-adjusted telomere length in the first percentile and/or a mutation in telomerase genes 2. One or more of the following cytopenia(s) Anemia 1. Symptomatic anemia with a hemoglobin < 9.5 g/dL or red cell transfusion requirements > 2 units/month for at least 2 months 2. Reticulocyte count < 60,000 /microL Thrombocytopenia 1. Platelet count < 30,000 /microL or < 50,000 /microL associated with bleeding 2. Decreased megakaryocytic precursors in the bone marrow Neutropenia 1. Absolute neutrophil count < 1,000 /microL OR 3. Idiopathic pulmonary fibrosis diagnosed by either a lung biopsy of high resolution computed tomography scan of the chest according to guidelines from the American Thoracic Society and European Respiratory Society 4. Age greater than or equal to 2 years 5. Weight > 12 kg Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy, or that death within 30 days is likely 2. Potential subjects with cancer who are on active chemotherapeutic treatment 3. Current pregnancy, or unwillingness to avoid pregnancy if of childbearing potential 4. Not able to understand the investigational nature of the study or give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Recurrent Gliomas Patients with histologically proven malignant glioma who have progressive disease following standard treatment will be eligible for this protocol. Malignant glioma glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant glioma NOS (not otherwise specified). Additionally, patients with primitive neuroectodermal tumors (PNETs) of the central nervous system, progressive low-grade gliomas and radiographically diagnosed brain stem gliomas will be eligible. 2. Patients must have unequivocal evidence for tumor progression by MRI or CT scan. This scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, that is., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. 3. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: A. They have recovered from the effects of surgery. B. Residual disease following resection of recurrent tumor is not mandated for into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, and within 14 days of registration, and on a steroid dosage that has been stable for at least 5 days. If the 96 hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days. 4. Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry. 5. All patients or their previously designated LAR (Legally Authorized Representative) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients will be registered prior to starting the study. 6. Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks. 7. Patients must have a Karnofsky performance status of greater than or equal to 60. 8. Patients must have recovered from the toxic effects of prior therapy: 2 weeks from any noncytotoxic investigational agent, 4 weeks from prior cytotoxic therapy, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, for example., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. 9. Patients must have adequate bone marrow function (WBC greater than or equal to 3,000/microl, ANC greater than or equal to 1,500/mm(3), platelet count of greater than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (SGOT and bilirubin less than or equal to 2 times ULN), and adequate renal function (creatinine less than or equal to 1.5 mg/dL and/or creatinine clearance greater than or equal to 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. level for hemoglobin may be reached by transfusion. 10. Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy. 11. This study was designed to women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No to this study will be based on race. 12. Patients must practice adequate contraception. 13. Prior treatment with an enzyme inducing antiepileptic drug must have been discontinued at least 14 days prior to study entry for Group A patients Patients who, in the view of the treating physician, have significant active cardiac, hepatic, or renal diseases are ineligible. 2. No concurrent use of other standard chemotherapeutics or investigative agents. 3. Prior treatment with platinum-based therapy. 4. Patients known to have an allergic response to mannitol. 5. Patients known to have an active malignancy other than their malignant glioma (except non-melanoma skin cancer or carcinoma in-situ of the cervix). 6. Patients who have an active infection requiring IV antibiotics. 7. Patients who are pregnant or breast feeding. 8. Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism. 9. QTc with Bazett's correction that is unmeasurable, or greater than or equal to 460 msec on screening ECG. If a patient has QTc greater than or equal to 460 msec on screening ECG, a second screen ECG may be repeated at least 24 hours apart. The average QTc from the 2 screening ECGs must be less than 460 msec in order for the patient to be eligible for the study. 10. EKG demonstrating clinically significant arrythmia (multifocal premature ventricular contraction [PVC], bigeminy, trigeminy, ventricular tachycardia, bradycardia) that is symptomatic or requires treatment (CTCAE Grade 3), or asymptomatic sustained ventricular tachycardia. 11. Patients who have baseline EKGs suggestive of past or present cardiac ischemia will not be eligible unless they have an appropriate (as defined by the P.I. of this trial) negative cardiac work up (that is, echocardiogram, stress test). 12. Patients may not be on systemic anti-coagulants (that is, heparin, warfarin, small heparin fragments)

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-75.0, Spinal Stenosis of Lumbar Region Low back pain and at least two of the following complaints in lower limbs: pain, weakness, burning or numbness that worsens with walking and improves with the cessation of walking decompensated diabetes mellitus Systemic hypertension and decompensated heart systemic disease affecting the lower limbs Neuromuscular Disease Use of steroids in the past 3 months Patients with previous surgery of the thoracic or lumbar spine cognitive disorder that interferes with the ability to understand or interpret the questionnaires Spondylolisthesis except degenerative degenerative scoliosis with Cobb angle of 10 °

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-100.0, High Grade Glioma Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma The diagnosis of GBM or Anaplastic Astrocytoma Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide Patients must be at least 12 months from completion of radiation therapy At least 2 months from completion of temozolomide (to be consistent with the the "rechallenge" group from Perry et al. JCO 2010) Age >18 years ECOG performance status <2 (Karnofsky >60%, see appendix A) There must be measurable disease on MRI Patients must have normal organ and marrow function as defined below Women must not be pregnant Must be able to receive an MRI Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment Patients may not have previously failed treatment with salvage temozolomide Patients may not have previously failed treatment with a VEGF inhibitor Patients may not have previously been treated with >1 course of radiotherapy Patients may not have previously been treated with radiosurgery to the brain Uncontrolled intercurrent illness Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Glioma Individuals aged 18-70 years with highly suspected (as assessed by study surgeon), newly diagnosed, untreated malignant glioma (see appendix 1) 2. Individuals with supratentorial gliomas with bodies involving in frontal lobe, temporal lobe, parietal lobe, occipital lobe or insular lobe 3. Individuals with the preoperative assessment that radiological radicality should be achieved 4. Individuals either with or without tumor in eloquent areas (see appendix 2) 5. Karnofsky performance scale 70 or more 6. All patients gave written informed consent. Appendix 1. Histological types（WHO 2007）: 1. Astrocytic tumours:Pilomyxoid astrocytoma 9425/3 Pleomorphic xanthoastrocytoma 9424/3 Diffuse astrocytoma 9400/3 Fibrillary astrocytoma 9420/3 Gemistocytic astrocytoma 9411/3 Protoplasmic astrocytoma 9410/3 Anaplastic astrocytoma 9401/3 Glioblastoma 9440/3 Giant cell glioblastoma 9441/3 Gliosarcoma 9442/3 2. Oligodendroglial tumours:Oligodendroglioma 9450/3 Anaplastic oligodendroglioma 9451/3 3. Oligoastrocytic tumours:Oligoastrocytoma 9382/3 Anaplastic oligoastrocytoma 9382/3 4. Ependymal tumours:Ependymoma 9391/3 Cellular 9391/3 Papillary 9393/3 Clear cell 9391/3 Tanycytic 9391/3 Anaplastic ependymoma 9392/3 Morphology code of the International Classification of Diseases for Oncology (ICD-O) {614A} and the Systematized Nomenclature of Medicine (http://snomen.org). Behaviour is coded /0 for benign tumours, /3 for malignant tumours and /1 for borderline or uncertain behaviour. Tumor grade: grade II~IV according to the latest WHO grading criteria; Appendix 2. Tumor location in eloquent areas: located in or close to areas of the dominant-hemisphere that associated with motor or language functions, including: 1. Frontal lobe, which divided into inferior frontal gyrus (BA44-Pars opercularis, BA45-Pars triangularis/Broca's area), middle frontal gyrus (BA9, BA46), superior frontal gyrus (BA4, BA6, BA8), primary motor cortex (BA4), premotor cortex (BA6), and supplementary motor area (BA6) 2. Parietal lobe, which divided into inferior parietal lobule (BA40-supramarginal gyrus, BA39-angular gyrus), parietal operculum (BA43), and primary somatosensory cortex (BA1, BA2, BA3) 3. Temporal lobe, which divided into transverse temporal gyrus (BA41, BA42), superior temporal gyrus (BA38, BA22/Wernicke's area), middle temporal gyrus (BA21) 4. Insular lobe Individuals with age < 18 years or > 70 years 2. Tumours of the midline, basal ganglia, cerebellum, or brain stem 3. Recurrent gliomas after surgery (except needle biopsy) 4. Primary gliomas with history of radiotherapy or chemotherapy 5. Contraindications precluding intraoperative MRI-guided surgery 6. Inability to give informed consent 7. KPS < 70 8. Renal insufficiency or hepatic insufficiency 9. History of malignant tumours at any body site 10. Tumour locations (in important eloquent area) do not enable complete resection of tumour

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 17.0-100.0, Sciatica Radiculopathy Lumbosacral radicular pain based on history and physical exam (e.g. pain radiating into one or both lower extremities, sensory loss, muscle weakness, positive straight leg raising test etc.) Numerical Rating Scale leg pain score > 4 (or if 3/10, greater or equal to back pain) MRI evidence of spinal pathology consistent with symptoms Untreated coagulopathy Previous spine surgery No MRI study Leg pain > 4 years duration Epidural steroid injection within past 3 years Cauda equina syndrome Previous failed trials with gabapentin or pregabalin Allergic reactions to gabapentin or pregabalin Referrals from surgery for diagnostic injections for surgical evaluation Serious medical or psychiatric that condition that might preclude optimal outcome or interfere with participation, such as the need for uninterrupted anticoagulation. Pregnancy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, High Grade Glioma Among the patients with high-grade glioma (glioblastoma multiforme or anaplastic astrocytoma), who received concurrent chemoradiation (CCRT) with temozolomide, the patients show the measurable enhancing portion (1 cm in the long diameter according to the RANO criteria) in the immediate f/up MRI after CCRT Among the patients with high-grade glioma (glioblastoma multiforme or anaplastic astrocytoma), who received concurrent chemoradiation (CCRT) with temozolomide, the patients do not show the measurable enhancing portion (1 cm in the long diameter according to the RANO criteria) in the immediate f/up MRI after CCRT

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 65.0-999.0, Glioblastoma Anaplastic Astrocytoma Histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma Age > 65 Karnofsky performance score > 60% Neutrophilic granulocyte count > 1500/µl Platelet count > 100 000/µl Hemoglobin > 10 g/dl Serum creatinine < 1.5 times the lab's upper normal limit AST or ALT < 3 times the lab's upper normal limit Alkaline phosphatase < 3 times the lab's upper normal limit No previous systemic chemotherapy Serious medical or neurological condition with a poor prognosis HIV infection Second cancer requiring radiotherapy or chemotherapy (contact the study coordinat if necessary) Hypersensitivity to temozolomide Conditions associated with regular vomiting that might affect oral administration of the drugs Psychological, familial, social or geographical circumstances with major implications for compliance with the study visit schedule Patient was taking part in other intervention studies within a month of starting this study

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-21.0, Anaplastic Astrocytoma Brain Stem Glioma Childhood Mixed Glioma Fibrillary Astrocytoma Giant Cell Glioblastoma Glioblastoma Gliosarcoma Untreated Childhood Anaplastic Astrocytoma Untreated Childhood Brain Stem Glioma Untreated Childhood Fibrillary Astrocytoma Untreated Childhood Giant Cell Glioblastoma Untreated Childhood Glioblastoma Untreated Childhood Gliosarcoma Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma, or fibrillary astrocytoma Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician Patient must be able to swallow oral medications to be eligible for study enrollment Karnofsky >= 50% for patients > 16 years of age or Lansky >= 50% for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score Patients must have not received any prior therapy other than surgery and/or steroids Absolute neutrophil count >= 1,000/mm^3 Platelets >= 100,000/mm^3 (unsupported) Hemoglobin >= 10 g/dL (unsupported) Total bilirubin =< 1.5 times upper limit of normal (ULN) for age Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy Patients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizure

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 3.0-75.0, Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Aplastic Anemia Burkitt Lymphoma Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Grade III Lymphomatoid Granulomatosis Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Congenital Amegakaryocytic Thrombocytopenia Diamond-Blackfan Anemia Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Paroxysmal Nocturnal Hemoglobinuria Peripheral T-cell Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Secondary Myelofibrosis Severe Combined Immunodeficiency Severe Congenital Neutropenia Shwachman-Diamond Syndrome Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Waldenstrom Macroglobulinemia Wiskott-Aldrich Syndrome Diagnosis of a histology documented hematologic malignancy or marrow disorder BONE Acquired bone marrow failure disorders aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) * Primary allogeneic HSCT is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully matched donor is available * Patients with PNH should not be eligible for a myeloablative HSCT Hereditary bone marrow failure disorders Diamond-Blackfan Anemia, Shwachman-Diamond Syndrome, Kostmann Syndrome, congenital Amegakaryocytic Thrombocytopenia; Fanconi Anemia or related chromosomal breakage syndrome, Dyskeratosis Congenital are excluded from this study die to their poor deoxyribonucleic acid (DNA) repair capacity * Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable * Dyskeratosis Congenita: diagnosis is supported by using either telomerase RNA component (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or X-linked DKC1 gene mutation Other non-malignant hematologic or immunologic disorders that require transplantation * Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia) * Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia) *Congenital primary immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies) ACUTE Subjects must be ineligible for or unable to receive a conventional myeloablative transplantation Resistant or recurrent disease after at least one standard combination chemotherapy OR first remission patients at high risk of relapse * Acute myeloid leukemia (AML) antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular mutations (e.g., fms-like tyrosine kinase3-internal tandem duplication [Flt3-ITD] mutation) * Acute lymphocytic leukemia (ALL) high or standard risk ALL (CML) Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation AND (MDS) Myelofibrosis (with/without splenectomy) with intermediate to high risk features Uncontrolled central nervous system (CNS) disease (for hematologic malignancies) Karnofsky (adult) or Lansky (for =< 16 years) performance status < 50% Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% predicted, corrected for hemoglobin and/or alveolar ventilation Left ventricular ejection fraction < 40% Bilirubin >= 3 X upper limit of normal Liver alkaline phosphatase >= 3 x upper limit of normal Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) >= 3 x upper limit of normal Child's class B and C liver failure Calculated creatinine clearance < 40 cc/min by the modified Cockroft-Gault formula for adults or the Schwartz formula for pediatrics Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs as follows: * Mediastinum: adult -40, pediatric (=<18 yrs)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, HIV-associated Myelopathy Documented history of HIV infection Age ≥ 18 Males and females are eligible. Subjects must agree to practice birth control or abstinence. Females of child-bearing potential must have a negative urine pregnancy within 14 days prior to study entry Adequate baseline organ function including the following laboratory values within 14 days prior to study entry Adequate liver function with ALT, AST and alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 2.5 mg/dL Creatinine < 2.3 Serum vitamin B12 level ≥ 200 pg/ml Diagnosis of HIVM by a neurologist defined as Presence of at least two of the following symptoms Paresthesias and/or numbness in the lower extremities or in all four limbs; Weakness of the limbs, with predominance in the lower extremities; Unsteady, stiff or uncoordinated gait; Sensation of electrical shock through the back or the legs upon flexion of the neck (L'Hermitte's sign); Stiffness or spasm in the lower extremities; Urinary frequency, urgency, incontinence or retention; Fecal incontinence or retention; Sexual dysfunction with erectile impairment in men Presence of acute, active, opportunistic infection, except oral thrush, orogenital or rectal herpes and MAI bacteremia within 2 weeks before randomization Evidence of another contributing cause for myelopathy Women who are pregnant, breast-feeding or planning a pregnancy Active abuse of drugs or alcohol, which in the opinion of the investigator would interfere with the subject's ability to comply with the protocol Any neurologic or systemic conditions, which in the opinion of the investigator would interfere with the evaluation of the subject Presence of significant cardiac, pulmonary or renal disease that would place the subject at risk for the fluid and protein load of IVIg History of hypersensitivity to immunoglobulin, or IgA deficiency; Vaccination with live viruses within the past 90 days; Patients receiving IVIg or other immunomodulatory agent (cyclosphosphamide, azathioprine, corticosteroids, tacrolimus, cyclosporine, OKT3, plasma exchange, alpha, beta or gamma interferon) within the past 3 months Patients in whom muscle dynamometry can not be performed for any reason

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 35.0-999.0, Postoperative Urinary Retention ≥ 35 years (Males & Females) Cervical Laminectomy Cervical Posterior Fusion Cervical Anterior/Posterior Fusion Lumbar Laminectomy Lumbar Posterolateral Fusion Lumbar Interbody Fusion < 35 years Cervical Anterior Discectomy and Fusion Cervical Anterior Corpectomy Cervical Posterior Discectomy Cervical Foraminotomy Lumbar Discectomy (METRx or Open) Lumbar Foraminotomy Lumbar Anterior Fusion Myelopathy with bladder dysfunction Patients currently taking an alpha-antagonist

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-999.0, Brain Tumor Patients must be > 18 years of age or older. 2. Patients must have histologically proven low grade astrocytoma,anaplastic astrocytoma, anaplastic mixed glioma, anaplastic oligodendroglioma,glioblastoma multiforme, astrocytoma WHO II,oligodendroglioma WHO II or mixed glioma WHO II. Patients do not haveto demonstrate progressive disease to participate in this study. 3. Patients must have completed initial glioma therapy involving radiation and be 3 months from the completion of radiation therapy. If initial glioma therapy did not radiation (example: anaplastic oligodendroglioma), then 2 cycles of chemotherapy must be completed prior to study entry. 4. Patients must be maintained on a stable corticosteroid regimen for > 5 days prior to entry. 5. Patients must have a Karnofsky performance status > 60% (i.e. the patient must be able to care for himself/herself with occasional help from others). 6. Patients must have adequate hematologic, renal and liver function (i.e. Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm3, creatinine > 1.5 mg/dl. 7. Women of childbearing potential must have a negative pregnancy test. 8. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be harmful to the developing fetus or nursing infant. Women of child-bearing potential must agree to use adequate contraception (either surgical sterilization; approved hormonal contraceptives such as birth control pills: Depo-Provera, or Lupron Depot; barrier methods such as condom or diaphragm along with spermicide; or an IUD). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and study PI immediately. 9. Ability to understand and the willingness to sign a written informed consent document Pregnant or breast feeding. 2. sexually active males and females unwilling to practice contraception during the study. 3. Serious concurrent infections. 4. Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months. 5. Patients with other serious uncontrolled co-morbid diseases that the investigator feels may comprise the study findings. 6. Allergic or sensitivity to sulfa containing medications

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Promyelocytic Leukemia (M3) Adult Nasal Type Extranodal NK/T-cell Lymphoma Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma Anaplastic Large Cell Lymphoma B-cell Adult Acute Lymphoblastic Leukemia Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt Lymphoma Contiguous Stage II Adult Diffuse Large Cell Lymphoma Contiguous Stage II Adult Lymphoblastic Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Cytomegalovirus Infection de Novo Myelodysplastic Syndromes Essential Thrombocythemia Extramedullary Plasmacytoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Isolated Plasmacytoma of Bone Monoclonal Gammopathy of Undetermined Significance Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Peripheral T-cell Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Central Nervous System Hodgkin Lymphoma Primary Central Nervous System Non-Hodgkin Lymphoma Primary Myelofibrosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Adult T-cell Leukemia/Lymphoma Stage I Chronic Lymphocytic Leukemia Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Multiple Myeloma Stage I Small Lymphocytic Lymphoma Stage IA Mycosis Fungoides/Sezary Syndrome Stage IB Mycosis Fungoides/Sezary Syndrome Stage II Adult Hodgkin Lymphoma Stage II Adult T-cell Leukemia/Lymphoma Stage II Chronic Lymphocytic Leukemia Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Multiple Myeloma Stage IIA Mycosis Fungoides/Sezary Syndrome Stage IIB Mycosis Fungoides/Sezary Syndrome Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Multiple Myeloma Stage III Small Lymphocytic Lymphoma Stage IIIA Mycosis Fungoides/Sezary Syndrome Stage IIIB Mycosis Fungoides/Sezary Syndrome Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Small Lymphocytic Lymphoma Stage IVA Mycosis Fungoides/Sezary Syndrome Stage IVB Mycosis Fungoides/Sezary Syndrome T-cell Adult Acute Lymphoblastic Leukemia T-cell Large Granular Lymphocyte Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Hairy Cell Leukemia Waldenström Macroglobulinemia HLA A*0201 subtype CMV seropositive Able and willing to sign the informed consent form (ICF) Willingness to be followed for the planned duration of the trial (6 months post-HCT) Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and active hepatitis B virus (HBV) (surface antigen negative) Planned related or unrelated HCT, with 8/8 or 7/8 (A, B, C, DRB1) high resolution HLA donor allele matching HCT for the treatment of hematologic cancers including, but not limited to Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status needs to be in hematologic remission by bone marrow/peripheral blood; persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography [PET] scan without progression is allowed) Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase Hodgkin and non-Hodgkin lymphoma A poor-risk patient, as defined by any of the following Chronic myelogenous leukemia in blast crisis Acute myeloid leukemia beyond second remission Multiple myeloma Aplastic anemia Planned immunosuppression with alemtuzumab or any equivalent in vivo T-cell depleting agent In vitro T cell depleted graft Planned prophylactic therapy with CMV immunoglobulin Planned CMV prophylactic therapy Experimental anti-CMV chemotherapy in the last 6 months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-60.0, Low Back Pain chronic low back pain (≥ 3 months) clinical suspicion of lumbo-sacral instability functional conventional radiographs of lumbar spine pain intensity > 4 / 10 on visual analogue scale age 20-60 years radicular pain pain at more than two locations lumbar spine surgery scoliosis lumbar spondylolysis lumbar spondylodiscitis anatomic aberrations of lumbar spine unconsolidated spine fractures neurologic deficits spine tumor

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-85.0, Osteoarthritis Patients with osteoarthritis scheduled for TKA at the department of orthopedic surgery, Hässleholm Hospital, Sweden, are eligible for participation in the study body mass index (BMI) > 35 m/kg2 prior major knee surgery to the ipsilateral knee ongoing infection, known immunological deficiency or ASA physical status category > IV

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Injuries Pain Subject is a veteran or active duty service member injured while on active military duty receiving care for pain related to the injury(ies) in the Department of Defense health care system or through the Department of Veteran's Affairs. 2. Subject is 18 years of age or older. 3. The elapsed time since the active-duty injury leading to chronic pain is not less than 3 months. 4. Subject reports constant or daily episodes of injury-related pain of at least moderate severity, graded 4 or higher on an 11-point NPRS (point estimate by subject and Investigator at time of enrolment based on overall pain or pain at a specific site). Pain may be nociceptive, neuropathic, or mixed. Phantom pain associated with amputation of an extremity or extremities is allowed. 5. Attempts to control pain with commercially available systemic analgesics have not provided adequate relief, in the judgment of the managing physician and subject. 6. Subject is able to localize site(s) of pain. At least one site of daily pain contributing to moderate severity (Inclusion Criterion 4) and intractability (Inclusion Criterion 5) must be in an extremity, or phantom pain at the site of an amputated extremity. If the extremity site of pain is not an amputated limb, then the pain must have a neuropathic component. This site is identified as the site of Target Pain (TP) for efficacy evaluations during the trial. 7. Subject is an acceptable candidate for surgical placement of an indwelling spinal cord stimulation device. 8. Subject is judged an appropriate candidate for treatment using the available techniques and interventions encompassed within the protocol's definition of comprehensive medical management. 9. For the duration of the trial, subject is willing to limit interventions for control of chronic pain to those approved by the Investigator. 10. The subject is judged psychologically appropriate for either treatment intervention, based on the impression of an interviewing psychologist or psychiatrist. 11. Subject provides informed consent Subject experiences phantom pain associated with amputation of both an upper and lower extremity. 2. Subject has headache or visceral truncal pain or other non-musculoskeletal pain as the only pain that results in constant or daily scores of ≥4 on the 11-point NPRS. 3. Subject has spinal disease that would, in the judgment of the investigator, preclude placement of a spinal cord stimulator. 4. Subject has ongoing chronic infection or a medical condition associated with an unacceptably increased risk of infection related to device implantation. 5. Subject has a current diagnosis or history of psychosis, cognitive impairment, hallucinations, or unexplained loss of consciousness, whether or not related to a combat injury that, in the opinion of the investigator, would the patient from participating in the trial. 6. Subject has a cardiac pacemaker. 7. Subject has any significant medical or psychiatric condition that would interfere with the conduct of the study or with the outcome measures. 8. Subject is pregnant or is breast feeding. 9. Subject has participated in any drug or device trial in the past 30 days. 10. Subject has any planned elective or semi-elective surgery during the 6 months of the Primary Treatment Phase, including stump revisions or grafting. 11. Subject has a psychological condition of great enough severity that it would unacceptably increase the medical risks associated with implantation and care of the devices required for the treatment on the CMM + SCS arm, or would likely interfere with the subject's ability to sustain participation in a research study of long duration. Investigators are encouraged to the medical monitor and the coordinating investigator in discussions about individual candidate subjects who have psychological diagnoses as part of the polytrauma syndrome before enrollment or treatment on this protocol

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Spinal Tumor STAGE 1: >/= 18 years old 2. STAGE 1: Pathologically confirmed diagnosis of cancer, including, but not limited to non-small cell lung cancer, breast, prostate, renal cell, melanoma, gastrointestinal, sarcoma, thyroid, head and neck primary, and carcinoma of unknown primary 3. STAGE 1: Signed informed consent 4. STAGE 2: 1-3 above, and Patients undergoing single fraction spinal SBRT STAGE 1: Patient with radiosensitive histologies (lymphoma, multiple myeloma, small cell carcinomas, germ cell tumors) 2. STAGE 1: Extensive (> 50%) height loss of the involved vertebral body 3. STAGE 1: Inability to tolerate lying flat on treatment table for greater than 30 minutes 4. STAGE 1: Pregnancy 5. STAGE 2: Prior irradiation of the spine site and level to be treated 6. STAGE 2: Patients with primary disease arising in the posterior elements of the VB in question 7. STAGE 2: History of Barrett's esophagus, esophageal webbing, stricture, or fistula 8. STAGE 2: Prior radiation to the esophagus

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Rheumatoid Arthritis Adult participants, >/=18 years of age who have completed the core study WA19926 and according to the investigator may benefit from RoActemra/Actemra treatment No current or recent adverse event or laboratory finding preventing the use of the study drug dose at baseline Receiving treatment on an outpatient basis Females who are pregnant Participants who have prematurely withdrawn from the core study WA19926 for any reason Treatment with any investigational drug since the last administration of the study drug in the core study WA19926 Treatment with an anti-tumor necrosis (TNF), anti-interleukin 1 agent or T-cell costimulation modulator since the last administration of the study drug in the core study WA19926 Immunization with live/attenuated vaccine since the last administration of the study drug in the core study WA19926 Diagnosis since the last WA19926 visit of rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis Abnormal laboratory values

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioma Have given written informed consent Have histological or cytological evidence of relapsed malignant glioma (such as glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma) for which no treatment of higher priority exists Available baseline tumor specimen is required prior to considering participant to be enrolled. The original diagnostic tumor tissue is sufficient for this but where possible, freshly obtained tumor biopsy material may be obtained Measurable disease to allow assessment of tumor response based on radiographic assessment following Macdonald and Response Evaluation In Solid Tumors (RECIST) Have sufficient hepatic, renal, and hematological function Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy or other investigational therapy for at least 30 days prior to study enrollment and recovered from the acute effects of therapy Able to swallow tablets and capsules For females, reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method (including intrauterine or barrier devices) during and for 3 to 6 months after the study Male participants must be willing to use contraception during and for 3 to 6 months after the study Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry Have moderate or severe cardiac disease Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second or third-degree atrioventricular block, bundle branch blocks, ventricular hypertrophy, or recent myocardial infarction) Have major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of normal) Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast) Have current acute or chronic leukemia Women who are pregnant or lactating Have received prior nitrosourea (including lomustine) therapy

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Mutliforme Age: 18 years or older Histological confirmation of supratentorial GBM KPS > 60 Neurological function 0 or 1 Adequate bone marrow as defined below absolute neutrophil count (ANC) > 1500 cells/mm3 platelets > 100,000 cells/mm3 hemoglobin > 10g/dl Adequate renal function as defined below BUN < 25mg/dl within 14 days prior to study registration Margin of contrast-enhanced residual mass closer than 15mm from the optic chiasm or optic nerves Prior invasive malignancy, unless disease-free for >3years Recurrent or multifocal GBM Severe co-morbidities such as unstable angina transmural myocardial infarction within 6 months COPD at the time of registration Hepatic insufficiency Bacterial or fungal infection requiring IV antibiotics at the time of registration Acquired Immune Deficiency Syndrome (AIDS)

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Glioblastoma Multiforme Anaplastic Oligoastrocytoma Histologically proven high-grade glioma anaplastic astrocytoma or glioblastoma Age ≥ 18 years WHO performance status ≤ 2 Scheduled for re-irradiation of a high grade glioma The patient is willing and capable to comply with study procedure • Life expectancy < 3 months

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Anaplastic Ependymoma Be informed of the nature of the study and have provided written informed consent 2. At least 18 years of age 3. ECOG performance of 0, 1, or 2, or KPS (Karnofsky performance status) ≥ 60. 4. Pathological verification of a WHO grade 4 astrocytoma (glioblastoma or gliosarcoma), or WHO Grade 3 anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma. 5. Documented recurrent glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma after at least one failed treatment of chemotherapy and radiation 6. Expected survival of at least 3 months 7. At least 2-weeks from cytoreductive surgery, if performed, 4-weeks from bevacizumab or other chemotherapy (6-weeks if prior chemotherapy was nitrosourea) and 12-weeks from completion of radiotherapy. 8. Ability to undergo MRI scanning without and with imaging dye on a periodic basis as defined in the protocol 9. Preserved major organ functions, i.e: Blood leukocyte count ≥ 3.0 x 109/L Blood absolute neutrophil count ≥ 1.5 x 109/L Blood platelet count ≥ 100 x109/L Blood hemoglobin ≥ 100 g/L (transfusions are allowed) Plasma total bilirubin level ≤ 1.5 times the upper institutional limit (ULN) of the ‖normal‖ (i.e. reference) range Plasma AST (aspartate aminotransferase) or ALT ≤ 2.5 times upper institutional limit (ULN) of the ‖normal‖ range Plasma creatinine ≤ 1.5 times upper institutional limit (ULN) of the ‖normal‖ range 12-lead ECG with normal tracings; or changes that are not clinically significant and do not require medical intervention, and QTc < 500 ms At least seven (7) days off of medications which inhibit or induce CYP2C9 or CYP3A4 before first study treatment day Any or other major recent or ongoing disease that, according to the Investigator, poses an unacceptable risk to the patient 2. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within the past 14 days before randomization. (Patients with grade 2 constipation within the past 14 days could be re-screened if constipation decreases to ≤ grade 1 with optimal management of constipation.) 3. Coexisting uncontrolled medical condition. 4. Hepatitis B or Hepatitis C, or HIV infection requiring anti-retroviral therapy 5. Active malignancy other than basal cell skin cancer 6. Other active malignancy during the previous 3 years 7. Major surgical procedure within 4 weeks 8. Prior stereotactic or gamma knife radiosurgery or proton radiation, unless unequivocal progression by functional neuro-imaging (PET, dynamic MRI, MRS, SPECT) or by re-operation with documented histologic confirmation of recurrence. 9. Prior anti-tumor therapy, as follows: at least 12-weeks from radiation therapy; at least 4-weeks from prior treatment with temozolomide or bevacizumab, 6-weeks from BCNU or CCNU. 10. Women of child bearing potential (WOCBP) who do not consent to using acceptable methods of birth control (oral contraceptives, IUD). For purposes of this study, WOCBP any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal. 11. Medically uncontrolled Type 1 or Type 2 diabetes mellitus 12. Pregnancy or lactation 13. Current participation in any other investigational clinical trial within 4-weeks. 14. Eastern Cooperative Oncology Group (ECOG) performance status > 2 after optimization of medications (See Appendix 4) or KPS < 60 15. Anticipated Life expectancy less than 3 months 16. Contraindications to the investigational product or known or suspected hypersensitivity

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 75.0-999.0, Urinary Retention year or older women hospitalized in an internal medicine or geriatric ward and with a bladder catheter for less than 48 hours for acute urinary retention chronic urinary retention acute retention with an anatomical (pelvic tumor, pelvic surgery) or neurological cause (peripheral neuropathy, spinal cord compression, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease) catheter placed for another indication (pressure ulcer protection, urine output monitoring) patient at the end of life contra-indication to alpha-blockers

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Anaplastic Oligoastrocytoma Anaplastic Astrocytoma Glioblastoma Age: 18 years to 75 years newly diagnosed WHO III-IV glioma after operation and radiotherapy Karnofsky Performance Score ≥ 60 Adequate bone marrow, liver and renal function Ability of subject to understand character and individual consequences of the clinical trial Written informed consent anticipating survival ≥2 months Refusal to participate the study Known hypersensitivity or contraindication to temozolomide Incompletely radiation Pregnant or lactating females Malignant tumor other than brain tumor Contraindicated for MRI examination Unable to comply with the follow-up studies of this trial Purulent and chronic infected wounds Uncontrolled psychotic disorders or epilepsy

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Fatigue Diagnosed with glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma who are clinically stable and have completed radiation therapy (excluding stereotactic radiosurgery) > 21 days and =< 24 months prior to enrollment; NOTE: clinical stability will be defined as a stable or improved Karnofsky performance status (KPS) compared to the prior month >= 6 score on the worst fatigue question of the BFI (Brief Fatigue Inventory, question 3); it is not required for the patient to complete the entire BFI to meet this criterion Undergone surgery (gross total or subtotal resection) or biopsy and will have been treated with concurrent radiation therapy and chemotherapy as standard of care for glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma patients; Note: radiation must be completed, but chemotherapy is allowed; patients who are currently using Optune device will be eligible to participate in this trial Negative serum pregnancy test done =< 7 days prior to registration only for women determined to be of childbearing potential by their treating physician Ability to complete questionnaire(s) by themselves or with assistance Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2 or 3 Provide informed written consent Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) Stable dose of corticosteroid >= 14 days prior to registration

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Cauda Equina Syndrome Male or female >18 years or older Cauda equina spinal injury at least 12 months previously, with lower motor neuron bowel dysfunction and at least one of the following symptoms Spending 30 minutes or more attempting to defecate each day or every second day Episodes of fecal incontinence once or more per month Abdominal discomfort before or during defecation Coexisting major unresolved physical problems due to the injury Performance of transanal irrigation on a regular basis Evidence of bowel obstruction or active inflammatory bowel disease History of cerebral palsy, stroke, multiple sclerosis or diabetic polyneuropathy Previous colorectal or perineal surgery(excluding minor surgery such as hemorrhoidectomy) Pregnancy or lactation Immunosuppression Prior implant for sacral nerve stimulation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Breast Cancer Bone Metastasis Pain The patient must be 18 years of age or older 2. The patient must have histologically proven breast adenocarcinoma 3. Radiographic evidence of bone metastasis is required .Acceptable studies plain radiographs, radionuclide bone scans, computed tomography scans and magnetic resonance imaging 4. The patient must have pain that appears to be related to the radiographically documented metastasis 5. Patients receiving systemic therapy with Capecitabine to metastatic disease (according to health basket) 6. Patients must have an estimated life expectancy of 3 months or greater 7. Patients will be eligible for treatment of multiple metastases only if these can be included in no more than two treatment sites 8. Signed study specific informed consent 9. Karnofsky Performance Status > 40 10. Calculated Creatinine Clearance > 50 ml/min 11. ALT and AST no greater than 3 5 times the institutional normal; bilirubin and serum creatinine no greater than 1.5 times normal; ANC greater than 1500, and platelets at least 100,00 Prior radiation therapy or prior palliative surgery to the painful site 2. Impending fracture of the treatment site or planned surgical fixation of the bone 3. Patients with clinical or radiographic evidence of spinal cord or cauda equina compression 4. Patients receiving systemic radionuclides (strontium, samarium, etc.) within 60 days prior to registration

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Stroke have a chronic (six months or more) unilateral stroke be able to walk 10 meters independently with or without a cane present residual weakness at the affected lower limb have an activity tolerance of at least two hours with a rest period receptive aphasia incontinence unstable medical condition history of injury anesthesia at the lower limbs

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 30.0-60.0, Low Back Pain Clinical diagnosis of chronic or recurrent low back pain Six month or longer history of non-specific LBP Minimum 90 days in pain in the last six months Average pain score of past month ≥3 on a 0-10 numerical rating scale Red flags (tumor, metabolic diseases, Rheumatoid arthritis, osteoporosis, prolonged steroid use, pregnancy, back surgery) Evidence of nerve root compression (pain reproduction with SLR>45º, weakness of major lower extremity muscle group, decreased deep tendon reflexes at knee or ankle, decreased sensation to pinprick) Acute trauma to low back

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-21.0, Pilomyxoid Astrocytoma Pilocytic Astrocytoma Glioma, Astrocytic Optic Nerve Glioma Pleomorphic Xanthoastrocytoma Glioblastoma Multiforme Anaplastic Astrocytoma Gliosarcoma Diffuse Intrinsic Pontine Glioma DIPG Low-grade Glioma Brainstem Glioma Age > 1 year of age and ≤ 21 years of age 2. Diagnosis 2.1. Group A Low-grade Glioma Group: Histology: Biopsy-proven Pilocytic Astrocytoma Fibrillary Astrocytoma Pilomyxoid Astrocytoma Pleomorphic Xanthoastrocytoma Other low grade astrocytomas Children with optic pathway tumors must have evidence of progressive disease on MRI and/or symptoms of deteriorating vision or, progressive hypothalamic/pituitary dysfunction or, diencephalic syndrome or precocious puberty. Patients with relapsed low-grade gliomas who have been previously treated with chemotherapy will be eligible for the study provided they have not previously failed therapy with any of the chemotherapeutic agents used in this study. 2.2 Group B High-grade Glioma/Pontine Glioma Group: Histology: Biopsy-proven Anaplastic astrocytoma Glioblastoma multiforme Age < 1 year or > 21 years 2. Patients who have known allergy to mebendazole or benzimidazole class drugs. 3. Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection . 4. Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy. 5. Pregnant female patients are not eligible for this study. Pregnancy tests with a negative result must be obtained in all post-menarchal females. 6. Lactating females must agree they will not breastfeed a child while on this study. 7. Males and females of reproductive potential may not participate unless they agree to use an effective contraceptive method and continue to do so for at least 6 months after the completion of therapy. 8. Patients who are unable to take oral medications because of significant vomiting will be excluded. 9. Group A Low-grade Glioma Group ONLY: Patients who have failed prior chemotherapy with vincristine, carboplatin, or temozolomide for this tumor are excluded. Patients with Neurofibromatosis Type 1 10. Group B High-grade Glioma/Pontine Glioma Group ONLY: Patients who failed prior chemotherapy with bevacizumab or irinotecan for this tumor are excluded. Patients who progressed on or within 12 weeks after completion of radiotherapy are excluded. Patients with a history or current condition that would preclude the use of bevacizumab

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-70.0, Adult Stem Cell Proliferation Healthy men and women Age 50 to 70 years old Ability to walk on a treadmill for 15 minutes Age less than 50 or greater than 70 years of age A history of difficult veins/difficulty obtaining blood samples Unwilling to follow the procedures of the trial Participated in more than 2 sessions per week of strenuous exercise in the last month Unable to tolerate the ingredients in NutraStem® or placebo, or have food allergies Intentionally lost or gained 10 or more pounds of body weight in the last 3 months Acute illness Severe co-morbid disease Use of any prescription or non-prescription products for antioxidant regimen or stem cell supplement within the past 4 weeks Diabetic

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-999.0, Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Histologically proven anaplastic oligodendroglioma or oligoastrocytoma Progressed or relapsed after surgery or radiation therapy Female or male aged 20 years or over At least 1 measurable mass lesion ECOG performance status 0-3 Adequate organ function absolute neutrophil count > 1,500/μL platelet count > 75,000/μL hemoglobin greater than 9 g/dL or 900g/L serum creatinine less than 1.5 times the upper limit of laboratory normal Prior course of temozolomide Combined glioblastoma Pregnant woman

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Astrocytoma Oligodendroglioma Oligoastrocytoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Glioblastoma Brain Tumors Brain Cancer Inclusion/ years of age Brain tumor(s) to be resected for clinical reasons Histological pathology confirmation that tumor is of glial origin, WHO Grade II, III or IV Adequate tissue available for processing as determined by Pathology Adequate decision making ability to review, discuss and sign a consent form to allow their tumor samples to be used for future human brain tumor biology laboratory research. Determination of capacity to consent is made by one of the co-investigators based on clinical assessment Patients opting for the standard treatment regimen for their disease as well as ongoing clinical trials will be are eligible to participate in this study. Standard care for newly-diagnosed glioblastomas typically consists of surgical resection followed by radiotherapy with concomitant temozolomide, followed by adjuvant temozolomide chemotherapy

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 16.0-999.0, Ewing Sarcoma Rhabdomyosarcoma Histologically confirmed Ewing's sarcoma Ewing's sarcoma must have progressed following at least one standard prior chemotherapy regimen Life expectancy of at least 16 weeks Willing to comply with the protocol for the duration of the study including pre and post-treatment biopsies, undergoing treatment, scheduled visits and examinations including follow up Presence of measurable disease Prior approval from insurance company to obtain oral temozolomide for the duration of the study Involvement in the planning and/or conduct of the study Previous enrollment in the present study Participation in another clinical study with an investigational product during the 21 days prior to first dose of olaparib and temozolomide Receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment Concurrent use of the following classes of inhibitors of CYP3A4: azole antifungals, macrolide antibiotics, protease inhibitors Persistent clinically significant toxicities caused by previous cancer therapy Previously documented diagnosis of myelodysplastic syndrome (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia Symptomatic uncontrolled brain metastases Major surgery within 14 days of starting study treatment Considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-999.0, Pediatric Brain Tumor Glioma Anaplastic Astrocytoma Medulloblastoma Glioblastoma Subject, parent, or guardian willing and able to give informed consent Recurrent or progressive pediatric brain tumor, with MRI evidence of disease Age at first diagnosis of brain tumor 1-21 years old Lansky or Karnofsky performance score of at least 50 at diagnosis Pregnancy Prior intolerance to valproic acid History of use of temozolomide Use of enzyme inducing anticonvulsant medications (see appendix B) Known urea cycle disorder (e.g. ornithine transcarbamylase deficiency)

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Patients With Severe Chronic Pain Patient is at least 18 years of age at the time of study entry Patient who has severe chronic pain, whom IT therapy is warranted, and who is intolerant of, or refractory to other treatments, such as systemic analgesics, adjunctive therapies, and/or IT morphine Patient is planned to be initiated on IT as the sole agent in the pump at a participated site Patient has not received treatment administered continuously via Medtronic SynchroMed® II pump within the past 30 days Patient has a life expectancy >6 months as determined by the physician Patient is able to read, understand, and voluntarily sign the IRB-approved informed consent document prior to the performance of any study-specific procedures Patient is able to understand and complete required assessments Patient has a known hypersensitivity to or any of its formulation components Patient has a pre-existing history of psychosis Patient has infection at the microinjection site, uncontrolled bleeding diathesis, or known spinal canal obstruction that impairs circulation of cerebrospinal fluid Patient is being initiated with in conjunction with other IT agents Patients with any other concomitant treatment or medical condition that, in the opinion of the clinician, would render IT administration hazardous

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 15.0-999.0, Solid Tumors Glioblastoma Patients must have histological or cytological evidence of a solid neoplasm Patients enrolled in the expansion cohort must have at least one measureable lesion as defined by the 1.1 for patients with systemic tumors or the RANO for patients with gliomas Patients with a systemic tumor must have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or no longer be candidates for standard therapy or have tumors for which there is no standard therapy Patients with a glioma must have Grade III (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) disease, Grade IV (glioblastoma) disease, or diffuse intrinsic pontine glioma (DIPG) and have received prior therapy including radiation and drug therapy and have documented recurrent disease as defined in the RANO criteria Patients with active infection or with a fever > 38.50 C within 3 days of the first scheduled day of dosing Patients with symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable Patients with known hypersensitivity to any of the components of CBL0137 Patients who are receiving concurrent anticancer therapy Patients receiving enzyme-inducing antiepileptic agents within 14 days prior to the start of study therapy Males with mean QTcF values of > 450 msec and females with QTcF values of > 470 msec following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG; Please speak with the PI for the complete Inclusion/Exclusion listing

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-999.0, Cerebrovascular Accident Stroke Cerebral Infarction Brain Infarction Brain Ischemia Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Have been admitted to a hospital unit for stroke rehabilitation Within 10 weeks post-stroke years or older Are experiencing difficulty walking Requires greater than one person assist for transfer or ambulation Have uncontrolled medical condition or another serious medication condition in addition to stroke Unable to understand or follow directions

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Malignant Glioma Patients must have histologically confirmed diagnosis of malignant glioma (Glioblastoma, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma) who may or may not be chemotherapy naïve and who are scheduled to receive radiotherapy (for a total of 60 GY) and concomitant daily temozolomide therapy (at a dose of 75 mg/m2 for one complete six week cycle). 2. Age ≥ 18 years 3. Karnofsky ≥ 60% 4. Hematocrit > 29%, ANC >1,000 cells/mm3, platelets > 100,000 cells/ mm3 5. Serum creatinine < 1.4 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal 6. For patients on corticosteroids, they must have been on a stable dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible 7. Ability and willingness to give informed consent 8. If sexually active, patients will take contraceptive measures for the duration of the treatments 9. Negative serum pregnancy test 48 hours prior to beginning study drug Pregnancy or breastfeeding 2. Co-medication that may interfere with study results; e.g., immune-suppressive agents other than corticosteroids 3. Inability or unwillingness to cooperate with the study procedures 4. Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of radiation therapy through the full course of radiation therapy is prohibited, with the exception of the study drug. Corticosteroids will be allowed for treatment of cerebral swelling. Rescue medication for treatment of nausea and vomiting is permitted after radiation therapy at the discretion of the investigator 5. Previous participation in any clinical trial involving granisetron 6. Any vomiting, retching, or NCI Common Toxicity version 4.0 grade 2-4 nausea in the 24 hours preceding radiation and chemotherapy 7. Ongoing vomiting from any organic etiology 8. Radiotherapy of abdomen within one week prior to or during the study 9. Received granisetron within 14 days prior to study enrollment 10. Prior and concomitant cancer chemotherapy and radiotherapy

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Stroke Inpatient at Caulfield Hospital Neurological Rehabilitation Unit at the time of recruitment Diagnosis of first stroke Presence of lower limb weakness determined by >10% difference in knee extensor strength between sides Functional Ambulation Category (FAC) > 3 Can walk a minimal distance of 14 metres (to allow measurement on a 10metre walk test (10MWT) Participants who meet all the except for their FAC score will have their FAC score re-measured on a weekly basis until they reach a score of greater than or equal to 3, at which point they become eligible and will be approached for recruitment Unable to provide informed consent (determined by consultation with rehabilitation consultant and the team neuropsychologist) Other diagnosed central nervous system disorder affecting mobility Active oncological diagnosis Unstable medication condition such as unstable diabetes or unstable cardiac condition that would prevent participation in cardiovascular activity Recent orthopaedic trauma and/or osteoarthritis that would limit participation in physical exercise Not willing to continue to attend the program if they discharge home before the end of the six week program

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 7.0-999.0, Limb Girdle Muscular Dystrophy Type 2D (LGMD2D) Subjects age 7 or older; cohort 1A must be adult and wheelchair-dependent Proven alpha-sarcoglycan deficiency by muscle biopsy or DNA testing Onset of weakness by 5 years age based on history of difficulty running, jumping and climbing stairs Subject enrolled in Cohort 1A must be adult and wheelchair dependent Subjects enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (i.e. a Gowers' sign, use a handrail for climbing stairs) and walk ≤ 80% of predicted distance on the 6MWT based on normative data Males and females of any ethnic group will be eligible Ability to cooperate with muscle testing Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate), during the first six months after gene therapy (females) or until two negative sperm samples are obtained post gene transfer (males) Active viral infection based on clinical observations The presence of SGCA mutations without weakness or loss of function Symptoms or signs of cardiomyopathy, including Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs Echocardiogram with ejection fraction below 40% Serological evidence of HIV infection, or Hepatitis A, B or C infection Diagnosis of (or ongoing treatment for) an autoimmune disease Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm) Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer Pregnancy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-65.0, Adult Lymphoblastic Lymphoma Disease ALL in complete remission (CR) at the time of transplant. Remission is defined as "less than 5.0% bone marrow lymphoblasts by morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration Philadelphia chromosome positive ALL is allowed Lymphoid blastic crisis of CML will be included (provided that patients achieve CR) Age Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen Organ Function All organ function testing should be done within 28 days of study registration Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula: CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL) Hepatic Non-compliant to medications No appropriate caregivers identified HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive Active life-threatening cancer requiring treatment other than ALL Uncontrolled medical or psychiatric disorders Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration Active central nervous system (CNS) leukemia Preceding allogeneic HSCT Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed

0