Datasets:

anthonyyazdaniml

/

CT-ADE-SOC

like 1

NCT00000134

NCT00000134_EG000

No

All

Adult | Older Adult

Phase 3

inclusion criteria: Males and females eligible for the CRRT must have been age 18 years or older and have had AIDS and CMV retinitis. They must have had active CMV despite a minimum of 28 days of previous treatment with an anti-CMV drug. Furthermore, they must have had an absolute neutrophil count greater than or equal to 500 cells/µL, platelet count greater than or equal to 20,000 cells/µL, and a serum creatinine < 2.5 mg/dL in order to tolerate the drug regimens. exclusion criteria: history of intolerance to ganciclovir or foscarnet, history of therapy involving the combination of foscarnet and ganciclovir, unwillingness to practice appropriate birth control, active drug or alcohol abuse, media opacity, retinal detachment not scheduled for surgical repair

intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day

Foscarnet

O=C(O)P(=O)(O)O

J05AD01

NCT00000134

NCT00000134_EG001

No

All

Adult | Older Adult

Phase 3

inclusion criteria: Males and females eligible for the CRRT must have been age 18 years or older and have had AIDS and CMV retinitis. They must have had active CMV despite a minimum of 28 days of previous treatment with an anti-CMV drug. Furthermore, they must have had an absolute neutrophil count greater than or equal to 500 cells/µL, platelet count greater than or equal to 20,000 cells/µL, and a serum creatinine < 2.5 mg/dL in order to tolerate the drug regimens. exclusion criteria: history of intolerance to ganciclovir or foscarnet, history of therapy involving the combination of foscarnet and ganciclovir, unwillingness to practice appropriate birth control, active drug or alcohol abuse, media opacity, retinal detachment not scheduled for surgical repair

intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day

Ganciclovir

Nc1nc2c(ncn2COC(CO)CO)c(=O)[nH]1

J05AB06 | S01AD09

NCT00000142

NCT00000142_EG000

No

All

Child | Adult | Older Adult

Phase 2 | Phase 3

Inclusion criteria: diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) 13 years or older Diagnosis of CMV (cytomegalovirus) retinitis as determined by a SOCA-certified Ophthalmologist. At least one lesion whose size is one-quarter disc area or more that can be photographed. Visual acuity in an affected eye of 3 or more lines on the (ETDRS) Early Treatment Diabetic Retinopathy Study chart at 1 meter distance (Snellen equivalent 8/200). score of 60 or more on the Karnofsky scale. Serum creatinine of 1.5mg/dL or less less than 1+ proteinuria on urinalysis Total bilirubin of 3.0 mg/dL or less Hepatic transaminase levels that do not exceed 5 times the normal levels Absolute neutrophil count of 750 cells/µL or greater Platelet count of 50,000 cells/µL or greater Hemoglobin of 7.5 g/dL or greater Negative pregnancy test (females of childbearing potential) All men/women of childbearing potential should practice birth control to prevent pregnancy while on study and for 3 months afterwards Willingness/ability, with the assistance of a caregiver if necessary to comply with treatment and follow-up procedures Signed consent statement Exclusion criteria: Evidence of a CMV (cytomegalovirus) retinitis lesion within zone 1. A lesion less than 1,500 µ from the margin of the optic disc or less than 3,000 µ from the center of the fovea in either eye excludes a patient. Evidence of a CMV retinitis lesions that involves 25% or more of the retinal area regardless of location. Previous or ongoing therapy for CMV (cytomegalovirus) disease with ganciclovir, foscarnet, CMV hyperimmune immunoglobulin, or other investigational agents solely as prophylaxis are eligible for enrollment. Retinal detachment(s) in the affected eye(s) media opacity that precludes visualization of the fundus of both eyes. patients with a diagnosis of extraocular CMV (cytomegalovirus) disease. Patients with history of clinically significant renal disease or renal dialysis. Patients with history of clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or arrhythmia. pregnant or lactating patients with active medical problems including drug or alcohol abuse which could hinder compliance with treatment or follow-up procedures. patients receiving therapy within the previous 7 days with nephrotoxic drugs, including: Amphotericin B, Vidarabine, Aminoglycoside antibiotics, Intravenous pentamidine. Patients receiving any of these drugs must discontinue the drug(s) at least one week prior to the time of enrollment, and for the duration of the trial period. history of clinically significant probenecid allergy.

IV (in the vein) treatment deferred until retinitis progressed, either: 5 mg/kg IV (in the vein) of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks, or 5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks. Cidofovir: Three groups: the deferral group, treatment deferred until retinitis progressed Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.

Cidofovir

Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1

J05AB12

NCT00000142

NCT00000142_EG001

No

All

Child | Adult | Older Adult

Phase 2 | Phase 3

Inclusion criteria: diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) 13 years or older Diagnosis of CMV (cytomegalovirus) retinitis as determined by a SOCA-certified Ophthalmologist. At least one lesion whose size is one-quarter disc area or more that can be photographed. Visual acuity in an affected eye of 3 or more lines on the (ETDRS) Early Treatment Diabetic Retinopathy Study chart at 1 meter distance (Snellen equivalent 8/200). score of 60 or more on the Karnofsky scale. Serum creatinine of 1.5mg/dL or less less than 1+ proteinuria on urinalysis Total bilirubin of 3.0 mg/dL or less Hepatic transaminase levels that do not exceed 5 times the normal levels Absolute neutrophil count of 750 cells/µL or greater Platelet count of 50,000 cells/µL or greater Hemoglobin of 7.5 g/dL or greater Negative pregnancy test (females of childbearing potential) All men/women of childbearing potential should practice birth control to prevent pregnancy while on study and for 3 months afterwards Willingness/ability, with the assistance of a caregiver if necessary to comply with treatment and follow-up procedures Signed consent statement Exclusion criteria: Evidence of a CMV (cytomegalovirus) retinitis lesion within zone 1. A lesion less than 1,500 µ from the margin of the optic disc or less than 3,000 µ from the center of the fovea in either eye excludes a patient. Evidence of a CMV retinitis lesions that involves 25% or more of the retinal area regardless of location. Previous or ongoing therapy for CMV (cytomegalovirus) disease with ganciclovir, foscarnet, CMV hyperimmune immunoglobulin, or other investigational agents solely as prophylaxis are eligible for enrollment. Retinal detachment(s) in the affected eye(s) media opacity that precludes visualization of the fundus of both eyes. patients with a diagnosis of extraocular CMV (cytomegalovirus) disease. Patients with history of clinically significant renal disease or renal dialysis. Patients with history of clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or arrhythmia. pregnant or lactating patients with active medical problems including drug or alcohol abuse which could hinder compliance with treatment or follow-up procedures. patients receiving therapy within the previous 7 days with nephrotoxic drugs, including: Amphotericin B, Vidarabine, Aminoglycoside antibiotics, Intravenous pentamidine. Patients receiving any of these drugs must discontinue the drug(s) at least one week prior to the time of enrollment, and for the duration of the trial period. history of clinically significant probenecid allergy.

5 mg/kg IV (in the vein) of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks Cidofovir: Three groups: the deferral group, treatment deferred until retinitis progressed Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.

Cidofovir

Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1

J05AB12

NCT00000142

NCT00000142_EG002

No

All

Child | Adult | Older Adult

Phase 2 | Phase 3

Inclusion criteria: diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) 13 years or older Diagnosis of CMV (cytomegalovirus) retinitis as determined by a SOCA-certified Ophthalmologist. At least one lesion whose size is one-quarter disc area or more that can be photographed. Visual acuity in an affected eye of 3 or more lines on the (ETDRS) Early Treatment Diabetic Retinopathy Study chart at 1 meter distance (Snellen equivalent 8/200). score of 60 or more on the Karnofsky scale. Serum creatinine of 1.5mg/dL or less less than 1+ proteinuria on urinalysis Total bilirubin of 3.0 mg/dL or less Hepatic transaminase levels that do not exceed 5 times the normal levels Absolute neutrophil count of 750 cells/µL or greater Platelet count of 50,000 cells/µL or greater Hemoglobin of 7.5 g/dL or greater Negative pregnancy test (females of childbearing potential) All men/women of childbearing potential should practice birth control to prevent pregnancy while on study and for 3 months afterwards Willingness/ability, with the assistance of a caregiver if necessary to comply with treatment and follow-up procedures Signed consent statement Exclusion criteria: Evidence of a CMV (cytomegalovirus) retinitis lesion within zone 1. A lesion less than 1,500 µ from the margin of the optic disc or less than 3,000 µ from the center of the fovea in either eye excludes a patient. Evidence of a CMV retinitis lesions that involves 25% or more of the retinal area regardless of location. Previous or ongoing therapy for CMV (cytomegalovirus) disease with ganciclovir, foscarnet, CMV hyperimmune immunoglobulin, or other investigational agents solely as prophylaxis are eligible for enrollment. Retinal detachment(s) in the affected eye(s) media opacity that precludes visualization of the fundus of both eyes. patients with a diagnosis of extraocular CMV (cytomegalovirus) disease. Patients with history of clinically significant renal disease or renal dialysis. Patients with history of clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or arrhythmia. pregnant or lactating patients with active medical problems including drug or alcohol abuse which could hinder compliance with treatment or follow-up procedures. patients receiving therapy within the previous 7 days with nephrotoxic drugs, including: Amphotericin B, Vidarabine, Aminoglycoside antibiotics, Intravenous pentamidine. Patients receiving any of these drugs must discontinue the drug(s) at least one week prior to the time of enrollment, and for the duration of the trial period. history of clinically significant probenecid allergy.

5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks. Cidofovir: Three groups: the deferral group, treatment deferred until retinitis progressed Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.

Cidofovir

Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1

J05AB12

NCT00000143

NCT00000143_EG001

No

All

Child | Adult | Older Adult

Phase 3

Inclusion criteria: Age 13 years or older Diagnosis of AIDS according to current Centers for Disease Control and Prevention (CDC) definition Diagnosis of active CMV retinitis by a SOCA-certified ophthalmologist (involvement of any zone or amount of retina is allowed) Best corrected visual acuity of 20/100 or better in at least one eye At least one lesion 750 cells/µL or greater Platelet count 50,000 cells/µL or greater Willingness and ability, with the assistance of a caregiver if necessary to comply with treatment and follow up procedures Willingness of all men and women of childbearing potential to practice adequate birth control to prevent pregnancies during the study and for 3 months afterwards Collection of all baseline data within 5 days prior to randomization Signed consent statement Exclusion criteria: Media opacities that preclude visualization of the fundus of all otherwise eligible eyes Treatment for CMV retinitis with the ganciclovir intraocular implant within 9 months of study entry Medical problems or drug or alcohol abuse sufficient to hinder adherence to treatment or follow up procedures Unwillingness to refrain from breast-feeding during the study and for 3 months afterwards

cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week Cidofovir intravenous: intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week

Cidofovir

Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1

J05AB12

NCT00000378

NCT00000378_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: - Patients must have: Unipolar major depression (per Diagnostic and Statistical Manuel-IV criteria) with or without melancholia. Exclusion Criteria: - Patients with the following symptoms or conditions are excluded: Psychotic or atypical subtype of unipolar major depression.

patients randomized to sertraline 12 week trial does up to 200mgs Sertraline: 12 week trial dose up to 200mgs

Sertraline

CN[C@H]1CC[C@@H](c2ccc(Cl)c(Cl)c2)c2ccccc21

N06AB06

NCT00000378

NCT00000378_EG001

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: - Patients must have: Unipolar major depression (per Diagnostic and Statistical Manuel-IV criteria) with or without melancholia. Exclusion Criteria: - Patients with the following symptoms or conditions are excluded: Psychotic or atypical subtype of unipolar major depression.

patients randomized to nortriptyline dose adjusted to therapeutic level Nortriptyline: 12 week trial dose adjusted to therapeutic level

Nortriptyline

CNCCC=C1c2ccccc2CCc2ccccc21

N06AA10

NCT00000575

NCT00000575_EG000

No

All

Child

Phase 3

Inclusion criteria: Age 5 to 12 years at time of screening Chronic asthma as evidenced by one or more of the following historical findings for at least 6 months during the past year: Asthma symptoms at least 2 times per week 2 or more usages per week of an inhaled bronchodilator Daily asthma medication Current asthma symptoms either by diary symptom code of 1 or greater or am or pm PEFR less than 80% of personal best post-bronchodilator value by diary, on 8 or more days during the prn screening period Methacholine sensitivity: estimated PC20 FEV1 less than or equal to 12.5 mg/ml Consent of guardian and assent of child Ability to comply with trial for 5 - 6.5 years Exclusion criteria: Presence of one or more of the following confounding or complicating problems: Any other active pulmonary disease Any chronic condition presumed to interfere with the successful completion of the project or confound its interpretation Pulmonary function testing findings suggesting a ventilatory defect other than asthma, or evidence of existing irreversible lung damage Severe chronic sinusitis or nasal polyposis Introduction of or a change in allergen immunotherapy within the past month Use of more than 4 sprays of nasal steroids daily (only beclomethasone allowed) Pregnancy Current use of metoclopramide, ranitidine, or cimetidine Treatment for gastroesophageal reflux Participation in another drug study Evidence of severe asthma as indicated by one or more of the following: Two or more hospitalizations for asthma in the past year Six or more steroid bursts in the past year Demonstrated need for continuous use of glucocorticoids, either oral or inhaled When off inhaled O2-agonist for more than 4 hrs and theophylline for more than 24 hrs, FEV1 less than 65% predicted Intubation for asthma at any time in the past Need for 9 or more puffs/day of albuterol for each of 3 consecutive days (excluding preventive use prior to exercise), or nocturnal asthma awakenings more than 1.5 times per week on average, or average diary card symptom code greater than 2, or requirement for other medications to control asthma, during prn screening period Inability to perform 3 acceptable FVC maneuvers of which at least 2 reproducible FEV1s are within 10% of the largest FEV1 Inability to complete the methacholine challenge or methacholine PC20 FEV1 greater than 12.5 mg/ml Evidence that patient or family may be unreliable or non-compliant or may move from the metropolitan area before trial completion

Budesonide (Pulmicort), two 100 microgram puffs bid + two microgram puffs albuterol (Ventolin) prn

Budesonide

CCCC1OC2CC3C4CCC5=CC(=O)C=CC5(C)C4C(O)CC3(C)C2(C(=O)CO)O1

A07EA06 | D07AC09 | R01AD05 | R03AK07 | R03AK12 | R03AL11 | R03BA02

NCT00000575

NCT00000575_EG001

No

All

Child

Phase 3

Inclusion criteria: Age 5 to 12 years at time of screening Chronic asthma as evidenced by one or more of the following historical findings for at least 6 months during the past year: Asthma symptoms at least 2 times per week 2 or more usages per week of an inhaled bronchodilator Daily asthma medication Current asthma symptoms either by diary symptom code of 1 or greater or am or pm PEFR less than 80% of personal best post-bronchodilator value by diary, on 8 or more days during the prn screening period Methacholine sensitivity: estimated PC20 FEV1 less than or equal to 12.5 mg/ml Consent of guardian and assent of child Ability to comply with trial for 5 - 6.5 years Exclusion criteria: Presence of one or more of the following confounding or complicating problems: Any other active pulmonary disease Any chronic condition presumed to interfere with the successful completion of the project or confound its interpretation Pulmonary function testing findings suggesting a ventilatory defect other than asthma, or evidence of existing irreversible lung damage Severe chronic sinusitis or nasal polyposis Introduction of or a change in allergen immunotherapy within the past month Use of more than 4 sprays of nasal steroids daily (only beclomethasone allowed) Pregnancy Current use of metoclopramide, ranitidine, or cimetidine Treatment for gastroesophageal reflux Participation in another drug study Evidence of severe asthma as indicated by one or more of the following: Two or more hospitalizations for asthma in the past year Six or more steroid bursts in the past year Demonstrated need for continuous use of glucocorticoids, either oral or inhaled When off inhaled O2-agonist for more than 4 hrs and theophylline for more than 24 hrs, FEV1 less than 65% predicted Intubation for asthma at any time in the past Need for 9 or more puffs/day of albuterol for each of 3 consecutive days (excluding preventive use prior to exercise), or nocturnal asthma awakenings more than 1.5 times per week on average, or average diary card symptom code greater than 2, or requirement for other medications to control asthma, during prn screening period Inability to perform 3 acceptable FVC maneuvers of which at least 2 reproducible FEV1s are within 10% of the largest FEV1 Inability to complete the methacholine challenge or methacholine PC20 FEV1 greater than 12.5 mg/ml Evidence that patient or family may be unreliable or non-compliant or may move from the metropolitan area before trial completion

Nedocromil (Tilade), four 2 mg puffs bid + two 90 microgram puffs albuterol prn

Nedocromil

CCCc1c2oc(C(=O)O)cc(=O)c2cc2c(=O)cc(C(=O)O)n(CC)c12

R01AC07 | R03BC03 | S01GX04

NCT00000620

NCT00000620_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina) For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)

Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels <6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

ACARBOSE

[H]C(=O)[C@H](O)[C@@H](O)[C@]([H])(O[C@@]1([H])O[C@H](CO)[C@@]([H])(O[C@H]2O[C@H](C)[C@@H](N[C@@]3([H])C=C(CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)CO

A10BD17 | A10BF01

NCT00000620

NCT00000620_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina) For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)

Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

ACARBOSE

[H]C(=O)[C@H](O)[C@@H](O)[C@]([H])(O[C@@]1([H])O[C@H](CO)[C@@]([H])(O[C@H]2O[C@H](C)[C@@H](N[C@@]3([H])C=C(CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)CO

A10BD17 | A10BF01

NCT00001596

NCT00001596_EG000

No

All

Adult | Older Adult

Phase 2

INCLUSION CRITERIA For the portion of the protocol involving continuations of pirfenidone treatment, the criteria are simply previous enrollment in 97-HG-0085. For enrollment in the new clinical trial, the inclusion criteria involve enrollment in protocol 95-HG-0193, "Clinical and Basic Investigations into Hermansky-Pudlak Syndrome". This itself requires a diagnosis of HPS based upon molecular grounds or the electron microscopic demonstration of deficiency of platelet dense bodies. In addition, for protocol 97-HG-0085, patients must: Be over 18 years of age. Have an FVC greater than 50 percent and less than or equal to 85 percent of predicted OR a hemoglobin-corrected DL(co) greater than 35 percent and less than or equal to 80 percent of predicted, with no evidence of a pulmonary embolism. Have evidence of reduced exercise tolerance lasting longer than one week on either the St. George's Hospital Respiratory Questionnaire or the Dyspnea Perception Scale. FEV(1)/FVC greater than 80 percent of predicted after bronchodilators. No evidence of improvement in pulmonary fibrosis within the past year defined as an FVC increased by 10 percent or a DL(co) increased by 15 percent. Distance walked greater than or equal to 150 meters (492 feet) with oxygen saturation greater than or equal to 83 percent on less than or equal to 6 L/min. of oxygen during the 6-Minute Walk Test (6MWT). Be available, willing, and able to come to the NIH Clinical Center for admission every 4 months for three years. EXCLUSION CRITERIA History of clinically significant environmental exposure known to cause pulmonary fibrosis (including but not limited to drugs, asbestos, beryllium, radiation, domestic birds). An explanation for interstitial lung disease other than HPS, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, cancer. Diagnosis of any connective tissue disease including but not limited to scleroderma, systemic lupus erythematosus, rheumatoid arthritis. Listing on a lung transplantation waiting list. Pregnancy or lactation Cigarette smoking in the past 6 months History of ethanol abuse or recreational drug use in the past two years History of human immunodeficiency virus (HIV) or chronic viral hepatitis infection Chronic use of high-dose steroids (greater than 10 mg prednisone/day) Prior use of pirfenidone Use of any of the following within 28 days of enrollment: investigational therapy, cytotoxic/immunosuppressive agents other than corticosteroids (including but not limited to azathioprine, cyclosphosphamide, methotrexate, cyclosporine); cytokine modulators (including but not limited to etanercept and infliximab); therapies targeted to treat pulmonary fibrosis (including but not limited to D-penicillamine, colchicine, interferon gamma-1b, bosentan, N-acetylcysteine Any severe medical complication including but not be limited to uncontrolled seizures, repeated transient ischemic attacks, abnormal mental status, severe ataxia, uncontrolled migraine headaches, diplopia, repeated episodes of syncope, untreated clinical depression, recent myocardial infarction (past 6 months), unstable angina, clinically relevant arrhythmias, uncontrolled hypotension or hypertension (systolic blood pressure less than 80 or greater than 180 mm Hg), myocarditis, hepatomegaly (liver greater than 3 cm below the right costal margin), renal glomerular impairment (creatinine clearance less than 35 ml/min/1.73 m2, pancreatitis, toxic thyroiditis, malignancy (except basal cell carcinoma) Medications with a high frequency of life threatening side effects Significant laboratory abnormalities, including but not limited to serum potassium less than 3.0 or greater than 5.4 mEq/L, SGPT greater than 100 U/L, CK greater than 700 U/L, hemoglobin less than 9.0 g/dL, platelets less than 70 k/mm3, leucocyte count less than 2.0 k/microliter, or cholesterol greater than 400 mg/dL. For women of child bearing age, failure to have an effective method of birth control.

Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.

Pirfenidone

Cc1ccc(=O)n(-c2ccccc2)c1

L04AX05

NCT00002850

NCT00002850_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion: Patient must have a diagnosis of multiple myeloma confirmed by the presence of: Bone marrow plasmacytosis with >10% abnormal plasma cells or multiple biopsy-proven plasmacytomas, and at least one of the criteria below must be documented: Myeloma protein in the serum Myeloma protein in the urine (free monoclonal light chain) Radiologic evidence of osteolytic lesions (generalized osteoporosis qualifies only if the bone marrow aspirate contains >20% plasma cells) Patients must have no active infection during the prior seven days and be off all antibiotics for the prior seven days. Patients cannot have received radiotherapy during the preceding ten days. Primary therapy for multiple myeloma must start within three days after entry to this study. For purposes of eligibility for this study, myelosuppressive chemotherapy or high-dose dexamethasone based regimens are acceptable as primary therapy. The high-dose dexamethasone regimen must include, at a minimum, dexamethasone 40 mg per day days 1-4, 9-12, 17-20 for the first cycle and 40 mg per day on days 1-4 of the second cycle. Patients who are to receive dexamethasone alone or dexamethasone with thalidomide are among those eligible for this protocol. Patients must have a serum creatinine <5.0 mg/dl and not require dialysis at the time of study entry. If patients require dialysis after enrollment, they can continue on the protocol using the adjusted medication guidelines Written informed consent must be obtained prior to entry. Exclusion: - Patients with smoldering myeloma, history of hypersensitivity to fluoroquinolones or trimethoprim, bone marrow transplant or autologous stem cell rescue planned during the first two months of treatment, patients taking theophylline, or patients previously treated with chemotherapy or high-dose dexamethasone

trimethoprim-sulfamethoxazole: Begin oral Trimethoprim-sulfamethoxazole when they start chemotherapy for multiple myeloma. Assigned treatment consists of TMP-SMX (Septra® or Bactrim®) 1 DS tablet [TMP-SMX DS = 160 mg trimethoprim and 800 mg sulfamethoxazole] every 12 hours for two months..

Sulfamethoxazole

Cc1cc(NS(=O)(=O)c2ccc(N)cc2)no1

G01AE10 | J01EC01 | J01EE01 | J04AM08

NCT00002975

NCT00002975_EG000

No

All

Child | Adult | Older Adult

Phase 2

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Actinic keratoses Histologically proven superficial or nodular basal cell carcinoma (BCC), squamous cell carcinoma in situ (Bowen's disease), or microinvasive squamous cell carcinoma No nodular BCC greater than 4 mm thick that will not be surgically removed No carcinoma with uncertain margins requiring Moh's surgery PATIENT CHARACTERISTICS: Age: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No known photosensitivity disease No porphyria or hypersensitivity to porphyrins PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No prior treatment with systemic photosensitizer that would cause residual cutaneous photosensitivity during study participation

4-6h and 18-24h, 20%, ALA application of superficial and nodular epidermally-derived lesions using ca 633 nm laser irradiation

Aminolevulinic Acid

NCC(=O)CCC(=O)O

L01XD04

NCT00004146

NCT00004146_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must have measurable or non-measurable tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment) Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable steroid regimen (no increase for the last five days) Absolute neutrophil count >= 1500/mm^3 Platelets >= 100,000/mm^3 Hemoglobin concentration >= 9.0 g/dl Creatinine =< 1.7mg/dL Total bilirubin =< 1.2 mg/dl Transaminases =< 2 times above the upper limits of the institutional normal Estimated life expectancy greater than 2 months Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients, if female and of childbearing potential must have a negative serum beta-hCG test and must not be breast feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the drug outlined in this protocol with reasonable safety Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ; patients with prior malignancies must be disease-free for >= five years Exclusion Criteria: Patients must be able to comply with prescribed medical care Prior therapy for the brain tumor (except surgery) Prior treatment with antineoplastic agents, including CAI

CAI with RT carboxyamidotriazole : CAI : CAI 250 mg PO plus RT followed by 4wks CAI alone followed by 8wks CAI then MRI if stable or better continue until progression and then follow for survival radiation therapy :

Carboxyamidotriazole

NC(=O)c1nnn(Cc2cc(Cl)c(C(=O)c3ccc(Cl)cc3)c(Cl)c2)c1N

NCT00004563

NCT00004563_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Patients with limited or diffuse systemic scleroderma if they had evidence of active alveolitis on examination of bronchoalveolar-lavage (BAL) fluid (defined as neutrophilia of ≥3 percent, eosinophilia of ≥2 percent, or both)on thoracic high-resolution computed tomography (CT), any ground-glass opacity, Onset of the first symptom of scleroderma other than Raynaud's phenomenon within the previous seven years, An FVC between 45 and 85 percent of the predicted value Grade 2 exertional dyspnea according to the baseline instrument of the Mahler Dyspnea Index (as measured with the use of the magnitude-of-task component). Exclusion Criteria: A single-breath carbon monoxide diffusing capacity (DlCO) that was less than 30 percent of the predicted value, A history of smoking within the preceding six months, other clinically significant pulmonary abnormalities, Clinically significant pulmonary hypertension requiring drug therapy. Patients taking prednisone at a dose of more than 10 mg per day, those who had previously been treated for more than four weeks with oral cyclophosphamide or had received two or more intravenous doses, Patients who recently received other potentially disease-modifying medications.

Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram. Cyclophosphamide: Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.

Cyclophosphamide

O=P1(N(CCCl)CCCl)NCCCO1

L01AA01

NCT00004978

NCT00004978_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: HIV positive Have a CD4 cell count of 300 cells/mm3 or more within 45 days of study entry Are on combination anti-HIV therapy or are beginning anti-HIV therapy at the time of study entry Are at least 18 years old Exclusion Criteria: Have received IL-2 before Have cancer requiring chemotherapy Have evidence of active clinical disease within the past year for any AIDS-defining illness or certain other conditions such as herpes zoster or Chagas disease. (This study has been changed. Previously, patients were ineligible if they had a history of any AIDS-defining illness or certain other conditions.) Have used certain medications, such as corticosteroids or drugs affecting the immune system, in the 45 days before study entry Have a nervous system disorder requiring antiseizure medication Have an autoimmune or inflammatory disease such as inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), psoriasis, optic neuritis, or any autoimmune/inflammatory diseases with potentially life-threatening complications Are pregnant or breastfeeding

Subcutaneous recombinant interleukin-2 (rIL-2) therapy

Indinavir

CC(C)(C)NC(=O)[C@@H]1CN(Cc2cccnc2)CCN1C[C@@H](O)C[C@@H](Cc1ccccc1)C(=O)N[C@H]1c2ccccc2C[C@H]1O

J05AE02

NCT00005879

NCT00005879_EG001

Accepts Healthy Volunteers

Female

Adult | Older Adult

Phase 2

DISEASE CHARACTERISTICS: Current random fine needle breast aspiration (FNA) evidence of 1 of the following: Hyperplasia with atypia Hyperplasia without atypia but with a 10-year modified Gail risk of at least 4% Hyperplasia without atypia but with a BRCAPRO risk of at least 25% Hyperplasia without atypia but with a known mutation in BRCA1 or BRCA2 Hyperplasia without atypia but with a history of contralateral ductal carcinoma in situ or invasive breast cancer FNA must have been taken during days 1-14 of the menstrual cycle for premenopausal women Classified as ACR class I-III on mammogram with stepwedge within past 6 months If intact uterus and/or ovaries, must have color doppler transvaginal pelvic sonogram within past 6 months showing endometrial thickening no greater than 13 mm premenopausal or no greater than 8 mm postmenopausal No ovarian cysts felt to be possibly or probably non-physiologic that have not resolved to gynecologist's satisfaction on repeat sonogram Must agree to have or have had genetic counseling and genetic testing performed for BRCA1 and BRCA2 No active cancer (e.g., detectable disease) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Any Performance status: Not specified Life expectancy: At least 12 months Hematopoietic: Hemoglobin greater than 10 g/dL Granulocyte count greater than 1,000/mm^3 No deficiencies in protein C, protein S, or antithrombin III No activated protein C resistance Hepatic: Albumin greater than 3.0 g/dL Bilirubin less than 1.5 mg/dL AST less than 100 U/L Alkaline phosphatase less than 200 U/L Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No history of deep venous thrombosis not related to trauma or pregnancy No severe coronary artery disease No history of prior stroke Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study No other active cancer No retinal vein thrombosis No concurrent severe poorly controlled migraine No factor V Leiden mutation carrier PRIOR CONCURRENT THERAPY: Biologic therapy: At least 12 months since prior immunotherapy Chemotherapy: At least 3 months between completion of prior KUMC phase II difluoromethylornithine (DFMO) study and baseline aspiration At least 12 months since prior chemotherapy Endocrine therapy: Must not have started or stopped hormone replacement therapy or oral contraceptives within 6 months of baseline aspiration Must continue all hormone replacement therapy and/or oral contraceptives that were being taken at time of baseline aspiration At least 12 months since prior tamoxifen, raloxifene, or other antihormonal therapy Radiotherapy: At least 3 months since prior radiotherapy Surgery: At least 6 months between prior oophorectomy and baseline aspiration Other: At least 2 weeks since the start of other new medication that would be ingested for 1 or more months

LY353381, 20 mg daily arzoxifene: one tablet daily

Arzoxifene

COc1ccc(-c2sc3cc(O)ccc3c2Oc2ccc(OCCN3CCCCC3)cc2)cc1

NCT00005901

NCT00005901_EG000

No

All

Child

Phase 3

INCLUSION CRITERIA: Children enrolled in this study will be limited to those with Sillence types III and IV OI, as determined by clinical and genetic criteria. Most of the children who will be included in this study are already enrolled in the protocols Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in Osteogenesis Imperfecta (97-CH-0064) and Growth Hormone Therapy in Osteogenesis Imperfecta (92-CH-0034). Screening of candidates will be based on telephone interviews with a parent, and referral records to include: AP and lateral radiographs of the lower extremities and spine, and family, developmental, fracture and medical history. An NIH clinical screening evaluation will be performed for those children who appear to have a history consistent with OI under protocol 04-CH-0077, Screening of and Diagnosis of Patients with Connective Tissue Disorder . Patients admitted for this screening visit who are less than four years of age as well as those older than 4 years of age but not meeting the criteria for inclusion in the growth hormone protocol, protocol 92-CH-0034, will be considered for enrollment in protocol 97-CH-0064 (Evaluation and Intervention for Ambulation, Growth and Basilar Invagination in OI), those older than four years who meet the criteria will be considered for co-enrollment in protocol 92-CH-0034. The inclusion criteria for protocol 92-CH-0034 are as follows: patients must have a clinical/biochemical diagnosis of osteogenesis imperfecta types III or IV, height less than third percentile for age, and radiological evidence that long bone epiphyses have not yet fused. Patients are excluded from protocol 92-CH-0034 if they have scoliosis of greater than 40 degrees unless scoliosis has been stable over the past two years, or evidence of severe basilar invagination. Patients with previous exposure to bisphosphonates in outside trials will be considered for participation in this trial. EXCLUSION CRITERIA: Inability to comply with the visit schedule, maintenance of the physical therapy program, and ability to administer and comply with GH injections are central to our analysis of the outcomes of this study. Failure to comply with these conditions will constitute exclusion criteria. Pregnancy. Patients that have had or will have surgery to place instrumentation in the spine (i.e. result of spine fusion).

Subjects who received Pamidronate every 3 months for 3 years.

PAMIDRONIC ACID

NCCC(O)(P(=O)(O)O)P(=O)(O)O

M05BA03

NCT00005901

NCT00005901_EG001

No

All

Child

Phase 3

INCLUSION CRITERIA: Children enrolled in this study will be limited to those with Sillence types III and IV OI, as determined by clinical and genetic criteria. Most of the children who will be included in this study are already enrolled in the protocols Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in Osteogenesis Imperfecta (97-CH-0064) and Growth Hormone Therapy in Osteogenesis Imperfecta (92-CH-0034). Screening of candidates will be based on telephone interviews with a parent, and referral records to include: AP and lateral radiographs of the lower extremities and spine, and family, developmental, fracture and medical history. An NIH clinical screening evaluation will be performed for those children who appear to have a history consistent with OI under protocol 04-CH-0077, Screening of and Diagnosis of Patients with Connective Tissue Disorder . Patients admitted for this screening visit who are less than four years of age as well as those older than 4 years of age but not meeting the criteria for inclusion in the growth hormone protocol, protocol 92-CH-0034, will be considered for enrollment in protocol 97-CH-0064 (Evaluation and Intervention for Ambulation, Growth and Basilar Invagination in OI), those older than four years who meet the criteria will be considered for co-enrollment in protocol 92-CH-0034. The inclusion criteria for protocol 92-CH-0034 are as follows: patients must have a clinical/biochemical diagnosis of osteogenesis imperfecta types III or IV, height less than third percentile for age, and radiological evidence that long bone epiphyses have not yet fused. Patients are excluded from protocol 92-CH-0034 if they have scoliosis of greater than 40 degrees unless scoliosis has been stable over the past two years, or evidence of severe basilar invagination. Patients with previous exposure to bisphosphonates in outside trials will be considered for participation in this trial. EXCLUSION CRITERIA: Inability to comply with the visit schedule, maintenance of the physical therapy program, and ability to administer and comply with GH injections are central to our analysis of the outcomes of this study. Failure to comply with these conditions will constitute exclusion criteria. Pregnancy. Patients that have had or will have surgery to place instrumentation in the spine (i.e. result of spine fusion).

Subjects who received Pamidronate every 6 months for 3 years.

PAMIDRONIC ACID

NCCC(O)(P(=O)(O)O)P(=O)(O)O

M05BA03

NCT00005906

NCT00005906_EG000

No

Female

Adult | Older Adult

Phase 2

INCLUSION CRITERIA: Patients enrolled in the lymphangioleiomyomatosis natural history protocol who have symptoms associated with one of the following: lymphangioleiomyomas chylous pleural effusions peripheral lymph-edema chyloptysis protein-losing enteropathy chyluria Patients will be included in this protocol if symptoms are attributed to the above processes. Patients with malabsorption disorders, diabetes, hypo/hyperthyroidism, or other endocrine-related disorders will be included if justified clinically based on severity of symptoms. EXCLUSION CRITERIA: Hypersensitivity to somatostatin, octreotide or its analogues Patients with hepatitis B, hepatitis C, or other clinically significant liver diseases Transplant patients Pregnant women or women who are beast-feeding Patient or another responsible party is unable to give the subcutaneous injection Patient unwilling to be followed per the guidelines set forth Patients with decreased renal function (creatinine greater than 1.5) Patients with HIV infection Immunosuppressed patients

Patients with lymphangioleiomyomatosis and lymphatic tumors causing chylous effusions and abdominal pain

Mycapssa

CC(O)C(CO)NC(=O)C1CSSCC(NC(=O)C(N)Cc2ccccc2)C(=O)NC(Cc2ccccc2)C(=O)NC(Cc2c[nH]c3ccccc23)C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)N1

H01CB02

NCT00006101

NCT00006101_EG000

No

Male

Adult | Older Adult

Phase 2

Criteria for Eligibility Men between the ages of 35 and 70 with family history of prostate cancer, i.e., prostate cancer diagnosed in two first degree relatives before the age of 70 years. (First degree relatives include a brother, father, and son.) There will be occasions in which a second or even third degree relative will be eligible. Additional information regarding these criteria is provided below and in Attachment 1.) Two or more affected relatives of which at least 1 is a first degree relative or At least two affected relatives, both of which are at least a second degree relative or One first degree relative diagnosed with prostate cancer at age 55 or less. No history of invasive cancer within 5 years (though non-melanoma skin or papillary bladder cancer will not be reason to exclude a patient); no prior history of prostate cancer, no severe metabolic disorders or other life-threatening acute or chronic disease; no additional x-ray or chemotherapy anticipated. Men found to have localized prostate cancer (Gleason score ≤7) as part of the screening for the current trial, and opt for watchful waiting as their standard of care treatment for their condition, will be eligible to sign an additional consent form to continue with the randomization and on-study activities of this trial. On-study activities for these individuals will not differ from the on-study activities for the other men enrolled in this trial. Must not require a medically mandated special diet which precludes compliance with study requirements Not requiring regular use of anticoagulants on a regular basis. Prior use of chemoprevention agent(s) (such as Proscar) is allowed as long as the subject has been off the agent(s) for at least 3 months. Not currently participating in another prostate prevention trial. Absence of history of current documented or symptomatic gastric or duodenal ulcer within 12 months prior to study entry, or of significant kidney or liver disease. No chronic anemia (hematocrit < 35 volume %), leukopenia (WEB <4,000) with normal differential, or thrombocytopenia (platelets <100,000) and with serum creatinine <1.5 mg/dl, serum bilirubin <2.0 mg/dl, and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) <2× normal. Urinalysis should have <1+ protein, 0-3 casts, 0-5 white blood cell count (WBC) and red blood cell count (RBC). Absence of any condition that predisposes to difficulties with hearing, wound healing or repair. Must meet Southwest Oncology Group performance status criteria of 0-1 (0 = fully active, able to carry on all predisease activities without restriction [Karnofsky scale 90-100]; 1 = restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, i.e., light housework or office work [Karnofsky scale 70-80]. Subjects must be willing and able to keep required visits for study procedures and to complete study questionnaires. Patient must not have had radiation therapy in the pelvic area.

500mg/d for 12 months eflornithine: Take 500mg of DFMO per day for 12 months

Eflornithine

NCCCC(N)(C(=O)O)C(F)F

D11AX16 | P01CX03

NCT00006244

NCT00006244_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Patient must be less than 70 years old Patients with advanced Multiple Myeloma that meet the eligibility requirements for mobilization/debulking with Cytoxan/VP-16/G-CSF, Cytoxan/Taxol/G-CSF, or Cytoxan/G-CSF (according to protocol 506.03); if clinically indicated a lower dose of cytoxan than 4g/m2 may be used for mobilization based on the attending's discretion; also, if the patients had previously collected PBSC of sufficient number in the past and meet the other eligibility requirements, they may be entered on this study after approval by the PI Patients with advanced Multiple Myeloma that have an identical syngeneic twin for donation of PBSCs Patients have advanced Multiple Myeloma if they were diagnosed initially with stage II or III disease or had stage I disease that progressed after initial therapy or failed to respond to therapy Syngeneic Donor Inclusion: Donor and patient have adequate documentation that donor and recipient are syngeneic; including ABO typing, HLA typing and VNTR studies Donor > 20 kg Donor meets eligibility to donate according to Standard Practice Guidelines Exclusion Criteria: Patient's age >= 70 Karnofsky score less than 80 A left ventricular ejection fraction less than 50%; Patients with congestive heart disease, history of myocardial infarction (MI), coronary artery disease or any arrhythmia history Total bilirubin > 1.5 mg/ml (unless history of Gilbert's disease) Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2 x upper limit of normal Estimated creatinine clearance < 60 ml/min or creatinine serum > 2.0 mg/dl Pregnancy Seropositivity for human immunodeficiency virus Patients who cannot give informed consent Secondary malignancies other than basal cell carcinoma of the skin or carcinoma in situ within the last five years History of seizures or requirement for medicines, such as haldol, for controlling mental disorders Concurrent need for corticosteroid therapy Active connective tissue disease Pleural effusion, pericardial effusion or ascites Patients allergic to gentamicin Patients with positive PCR for hepatitis C or hepatitis B Patients with hypersensitivity to E. coli - derived preparations Patients with systemic infection at time of IL2 therapy Patients who previously have had more than 50% of their pelvic area irradiated Patients with pulmonary function tests that show diffusion capacity (corrected) < 60%, and/or forced expiratory volume in 1 second (FEV1) < 65% of predicted

Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Melphalan

N[C@@H](Cc1ccc(N(CCCl)CCCl)cc1)C(=O)O

L01AA03

NCT00008385

NCT00008385_EG001

No

All

Adult | Older Adult

Phase 3

RUN-IN PERIOD: Inclusion Criteria: Histologically confirmed, completely resected stage IA (pT1, N0) or IB (pT2, N0) non-small lung cancer (except carcinoid)* Completion of treatment for stage I lung cancer within the past 6 to 36 months and currently disease free At least one mediastinal lymph node sampled at resection NOTE: *Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B (CALGB) patients must be T1, N0; CALGB patients may be T2, N0 provided disease was completely resected prior to June 1, 2001 and participation in CALGB 9633 was refused if offered 18 years old and over Eastern Cooperative Oncology Group performance status 0-1 Bilirubin no greater than upper limit of normal (ULN) Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) no greater than ULN Prior mineral, herbal, phytochemical, or vitamin supplementation allowed Concurrent non-selenium containing mineral, herbal, phytochemical, or vitamin supplementation allowed if schedule and supplementation prior to study remains unchanged Exclusion Criteria: Evidence of new or recurrent lung cancer on chest x-ray within the past 8 weeks Synchronous lung or non-lung lesions or metastasis, even if resectable History of more than one primary lung cancer at any time Concurrent or other prior cancer within the past 5 years except localized non-melanoma skin cancer Prior or concurrent chemotherapy for recurrent lung cancer Prior or concurrent radiotherapy for recurrent lung cancer Concurrent surgery Concurrent supplement(s) containing more than 50 micrograms of selenium STUDY PHASE: Free of disease Consumed at least 75% of tablets during 4-week run-in period

Participants receive oral selenium yeast daily for 6 months. Treatment repeats every 6 months for 8 courses for a total of 4 years in the absence of unacceptable toxicity. selenium: Given orally

Selenium

[Se]

NCT00009945

NCT00009945_EG000

No

Female

Adult | Older Adult

Phase 3

Eligibility Patients must have undergone either a total mastectomy or a lumpectomy with either an axillary dissection or sentinel node biopsy. If any sentinel node is histologically positive by H & E, or histologically suspicious on H & E and confirmed positive by immunohistochemistry (IHC), then the patient must have a completion axillary dissection. The tumor must be invasive adenocarcinoma on histologic examination with clinical assessment T1-3, N0-1, M0. Patients must not be participating in any other clinical trials of systemic therapy for early-stage breast cancer. Patients may participate in the following radiation therapy trials: Node-positive patients may participate in the National Cancer Institute of Canada Clinical Trials Group protocol MA.20, provided the requirements of the B-34 protocol continue to be met. (Node-negative B-34 patients may not participate in MA.20.) Node-positive mastectomy patients may participate in Southwest Oncology Group protocol S9927, provided the requirements of the B-34 protocol continue to be met. Patients must have an analysis of both estrogen and progesterone receptors on the primary tumor performed prior to randomization. Tumors will be defined as ER or progesterone receptor (PgR) positive if: 1) the Dextran-coated charcoal or sucrose-density gradient method shows them to have greater than or equal to 10 fmol/mg cytosol protein, or 2) if using individual laboratory criteria they can be shown to be positive by the enzyme immunoassay method (EIA) or immunocytochemical assay. "Marginal or borderline," results (i.e., those not definitively negative) will also be considered positive. At the time of randomization, the patient must have had the following within the past 3 months: history and physical exam, a bone scan, thoracic and lumbar spine x-rays, and a chest x-ray. Within the past 12 months patients must have had a gynecologic exam (for women who have a uterus and who will be taking tamoxifen) and a bilateral mammogram. At the time of randomization: the postoperative absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3 (or less than 1500/mm3 if, in the opinion of the investigator, this represents an ethnic or racial variation of normal); the postoperative platelet count must be greater than or equal to 100,000; there must be postoperative evidence of adequate hepatic function, i.e., total bilirubin at or below the upper limit of normal (ULN) for the laboratory; and alkaline phosphatase less than 2.5 x the ULN; and the serum glutamate oxaloacetate transaminase (SGOT)/ aspartate transaminase (AST) less than 1.5 x the ULN; there must be postoperative evidence of adequate renal function (serum creatinine within or less than the laboratory's normal range). Serum albumin and serum calcium must be within normal limits. A patient with skeletal pain is eligible for inclusion in the study if bone scan and/or roentgenological examination fails to disclose metastatic disease. Suspicious findings must be confirmed as benign by x-ray, MRI, or biopsy. Patients with prior nonbreast malignancies are eligible if they have been disease- free for greater than or equal to 5 years before randomization and are deemed at low risk for recurrence by their treating physicians. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by surgery only, or lobular carcinoma in situ (LCIS) of the ipsilateral or contralateral breast treated by hormone therapy and/or surgery only are eligible, even if these were diagnosed within 5 years before randomization. Patients must have a Zubrod performance status of 0, 1, or 2. Special conditions for eligibility of lumpectomy patients: Irradiation and surgery. Patients treated by lumpectomy and axillary node dissection (or no axillary dissection if sentinel node biopsy is negative) to be followed by breast radiation therapy must meet all the eligibility criteria in addition to the following: Generally, lumpectomy should be reserved for tumors less than 5 cm. However, at the investigator's discretion, patients treated with lumpectomy for tumors greater than or equal to 5 cm are eligible. The margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS). For patients in whom pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins. This is permissible even if axillary dissection has been performed. Patients in whom tumor is still present at the resected margins after re-excision(s) must undergo total mastectomy to be eligible. Ineligibility. Significant non-malignant bone disease that is likely to interfere with the interpretation of bone x-rays. Ulceration, erythema, infiltration of the skin or the underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude. (Tethering or dimpling of the skin or nipple inversion should not be interpreted as skin infiltration. Patients with these conditions are eligible.) Ipsilateral lymph nodes that on clinical examination are found to be fixed to one another or to other structures (cN2 disease). Suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless there is biopsy evidence that these are not involved with tumor. Prior therapy for breast cancer, including irradiation, chemotherapy, biotherapy, and/or hormonal therapy, with the exception of tamoxifen. Tamoxifen may be given as adjuvant therapy before study entry, but only if it was started within 28 days before randomization. Patients who started tamoxifen within 28 days before randomization and who are being considered for chemotherapy must have their tamoxifen stopped at the start of chemotherapy. Prior history of breast cancer, except LCIS. Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible only if this therapy is discontinued prior to randomization.) Exceptions: patients may use low-dose estrogen vaginal creams or Estring® for symptomatic vaginal dryness, raloxifene (or other selective estrogen receptor modulators [SERMs]) for the prevention of osteoporosis, and luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists for the purpose of medical ovarian ablation as a component of adjuvant therapy for the breast cancer. Patients currently taking alendronate (Fosamax®) or other bisphosphonates or calcitonin to treat or prevent osteoporosis are not eligible. Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from being subjected to any of the treatment options or would prevent prolonged follow-up. Psychiatric or addictive disorders that would preclude obtaining informed consent. Pregnancy or lactation at the time of proposed randomization. This protocol excludes pregnant or lactating women because the effects of clodronate on such women have not been studied fully. Bilateral malignancy or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant. Special conditions for ineligibility of lumpectomy patients: Irradiation and surgery. The following patients will also be ineligible: Patients with diffuse tumors (as demonstrated on mammography) that would not be considered surgically amenable to lumpectomy. Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins. Patients in whom the margins of the resected specimen are involved with invasive tumor or ductal carcinoma in situ (DCIS). Additional surgical resections to obtain free margins are allowed. Patients in whom tumor is still present after the additional resection(s) must undergo mastectomy to be eligible.

Clodronate

CLODRONIC ACID

O=P(O)(O)C(Cl)(Cl)P(=O)(O)O

M05BA02

NCT00010439

NCT00010439_EG000

No

All

Child

Phase 2

Eligibility Criteria: 5-14 years of age Weight 20 kg or greater History of one or more atraumatic fracture Sexual development no greater than Tanner II Osteoporosis by DXA (Diagnosis of high-turnover osteoporosis with no underlying cause (e.g., malignancy, hyperthyroidism, hyperparathyroidism, or vitamin D intoxication) Inclusion Criteria: Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20%). Bone mineral density by DXA at 2 standard deviations (SD) below normal mean for age (Z-score at least 2 SD below normal mean at the lumbar spine or hip) Parental consent (and patient assent after age 12 years) to participate in the study. Sexual development at Tanner stage II or less (Prepubertal stage) Weight 20kg and more Exclusion Criteria: History of severe gastritis or reflux Marked kyphoscoliosis or inability to sit or stand for at least 30 minutes. Abnormalities of the esophagus that delay emptying (e.g., strictures or achalasia) Hypersensitivity to bisphosphonates Uncorrected hypocalcemia History of gastric or duodenal ulcers Renal dysfunction as indicated by serum Creatinine greater than 1.5 mg/dL Liver dysfunction as indicated by serum SGPT greater than 2 times upper limit of normal for age or serum total bilirubin greater than 2.0 mg/dL Diagnosis of osteogenesis imperfecta (including family history) or blue sclerae or deafness Diagnosis of active rickets, osteomalacia, or bone alkaline phosphatase > 2 times normal for age Severe gastritis or reflux Pregnancy Anorexia Nervosa Prior/Concurrent Therapy- Prior course of prednisone allowed No concurrent prednisone except inhaled steroids No concurrent high-dose glucocorticoids No concurrent salmon calcitonin No other concurrent bisphosphonates No concurrent long-term anti-seizure medication

Ten children will take alendronate 35mg or 70mg weekly depending upon the body weight for 12 months. Patients will also take calcium supplement daily.

ALENDRONIC ACID

NCCCC(O)(P(=O)(O)O)P(=O)(O)O

M05BA04 | M05BB03 | M05BB05 | M05BB06

NCT00016354

NCT00016354_EG000

No

All

Adult | Older Adult

Phase 1

DISEASE CHARACTERISTICS: Histologically confirmed malignancy Metastatic or unresectable No effective standard curative or palliative measures exist No known CNS or brain metastasis PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin normal SGOT/SGPT normal Renal: Creatinine normal Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled ventricular arrhythmia No myocardial infarction within the past 3 months No superior vena cava syndrome Neurologic: No grade 1 or greater peripheral neuropathy No uncontrolled major seizure disorder No spinal cord compression Other: No active serious infection requiring IV antibiotics No concurrent uncontrolled illness No concurrent unstable or serious medical condition No chronic diarrhea or malabsorption No history of allergic reactions to compounds similar in chemical or biological composition to benzoylphenylurea No psychiatric illness or social situation that would preclude study compliance Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent growth factors during first 2 courses of study Concurrent epoetin alfa allowed Chemotherapy: At least 28 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: At least 28 days since prior large-field radiotherapy Prior palliative radiotherapy for painful bone metastases allowed No concurrent radiotherapy, including palliative or whole-brain radiotherapy for CNS disease Surgery: At least 28 days since prior major surgery Other: No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational or commercial agents or therapies for the malignancy No other concurrent investigational agents Concurrent bisphosphonates allowed if bone metastases are not only site of measurable or evaluable disease

BPU, administered over a dose range of 5-320 mg

Benzoylphenylurea

NC(=O)N(C(=O)c1ccccc1)c1ccccc1

NCT00019747

NCT00019747_EG000

No

All

Adult | Older Adult

Phase 2

DISEASE CHARACTERISTICS: Diagnosis of recurrent or metastatic colorectal carcinoma previously resected within 12 weeks of study entry Surgical resection combined with radiofrequency ablation allowed PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: Hemoglobin at least 8.0 g/dL Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Partial thromboplastin time (PTT)/prothrombin time (PT) no greater than 120% of control (except in therapeutically anticoagulated nonrelated medical conditions [e.g., atrial fibrillation]) Total bilirubin no greater than 2.0 mg/dL (direct bilirubin no greater than 1.0 mg/dL for patients with Gilbert's syndrome) Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 2.5 times normal No history of hepatic cirrhosis No concurrent hepatic dysfunction Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No severe congestive heart failure or active ischemic heart disease No active clots within 1 year before diagnosis OR must be receiving concurrent treatment with anticoagulant (e.g., low molecular weight heparin or equivalent agent) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use 1 highly effective method of contraception AND 1 additional effective method of contraception for least 4 weeks before, during, and for at least 4 weeks after study participation No history of severe hypothyroidism No history of seizures No significant history of other medical problems that would preclude surgery No peripheral neuropathy greater than grade 1, except localized neuropathy due to a mechanical cause or trauma PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics Other: See Cardiovascular No concurrent sedating drugs that cannot be reduced to a minimal level No concurrent sedating recreational drugs or alcohol No concurrent antiseizure medications

Patients receive oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).

Thalidomide

O=C1CCC(N2C(=O)c3ccccc3C2=O)C(=O)N1

L04AX02

NCT00022672

NCT00022672_EG001

No

Female

Adult | Older Adult

Phase 3

Inclusion Criteria: postmenopausal women; metastatic breast cancer suitable for endocrine therapy; positive hormone receptor status; Human epidermal growth factor receptor 2 (HER2) overexpression. Exclusion Criteria: patients on hormone replacement therapy; previous chemotherapy for metastatic disease; uncontrolled cardiac disease and history of cardiac failure.

1 mg oral dose of anastrozole every day for 24 Months in the Main phase.

Anastrozole

CC(C)(C#N)c1cc(Cn2cncn2)cc(C(C)(C)C#N)c1

L02BG03

NCT00031447

NCT00031447_EG001

No

All

Child

Phase 3

Inclusion Criteria: Isolation by viral culture of herpes simplex virus (HSV)-1or HSV-2 from cutaneous lesions, conjunctivae, or oropharynx. Detection of HSV at any of these sites is sufficient, and the presence of skin lesions is not required for study enrollment. Normal cerebrospinal fluid (CSF) indices (<22 white blood cells (WBCs)/mm^3 and protein <115 mg/dl for term infants; (<25 WBCs/mm^3 and protein <220 mg/dl for preterm infants both at the time of diagnosis of HSV disease and at the time of study randomization. No evidence of HSV central nervous system (CNS) disease by computed tomography (CT) with contrast, magnetic resonance imaging (MRI) with gadolinium, or head ultrasound (HUS) [NOTE: CT with contrast is the preferred imaging study]. Normal electroencephalogram (EEG), if performed [NOTE: EEG is suggested for the evaluation of infants with HSV disease but is not required for this study]. No evidence of visceral dissemination of HSV infection (normal liver function tests, normal chest x-ray, etc.). Negative CSF HSV polymerase chain reaction (PCR) results from specimens obtained both within 72 hours of initiation of intravenous acyclovir therapy and within 48 hours prior to completion of intravenous acyclovir therapy. Less than or equal to 28 days of age at the time of initial presentation with skin, eyes, and mouth (SEM) disease. Birth weight greater than or equal to equal to 800 grams. Exclusion Criteria: Infants with either grade 3 or grade 4 intraventricular hemorrhage (IVH) prior to study enrollment. Breast feeding infants whose mothers are taking acyclovir, valacyclovir, or famciclovir for >120 hours (>5 days). If at any point following enrollment the mother takes these antiviral drugs for >120 hours (>5 days), she will be asked to refrain from breast feeding while taking the drug. Infants known to be born to women who are human immunodeficiency virus (HIV) positive (but HIV testing is not required for study entry). These infants are at known risk for acquiring HIV, which would alter their immune response to other infections, including HSV infection. Additionally, they may be receiving antiretroviral and/or antiviral drugs during the time in which the study of suppressive oral acyclovir is being conducted. As such, they will be excluded if the mother's positive HIV status is known at the time of evaluation for study inclusion. If at any point following enrollment it is learned that an infant is HIV positive, he/she will be continued on the study protocol. Infants with either central nervous system (CNS) or disseminated HSV infection. Patients with CNS HSV infection will be considered for enrollment and randomization in the ongoing Collaborative Antiviral Study Group (CASG) evaluation of oral suppressive acyclovir therapy following neonatal HSV infections involving the CNS. Infants with creatinine >1.5mg/dl at time of study enrollment. Infants receiving acyclovir expectantly do not qualify for this study because they never developed HSV disease. Expectant therapy describes infants who are cultured at approximately 24 hours of life because of a risk of HSV infection (i.e. they are born to women with active genital lesions). Oftentimes, if these cultures are positive, the infant will receive a course of intravenous acyclovir to prevent the development of HSV disease. However, since they never actually had HSV disease, their potential outcome cannot be compared with infants with typical skin, eyes, and mouth (SEM) disease, and so they are not included in this study.

Oral suspension 300 mg/m^2/dose TID for 6 months.

Acyclovir

Nc1nc2c(ncn2COCCO)c(=O)[nH]1

D06BB03 | D06BB53 | J05AB01 | S01AD03

NCT00031460

NCT00031460_EG000

No

All

Child

Phase 3

Inclusion Criteria: Viral Culture: If cutaneous lesions are present, then isolation of Herpes Simplex Virus (HSV)-1 or HSV-2 by viral culture from any site (skin, oropharynx, cerebral spinal fluid [CSF], urine, etc.) will be required for study entry. If cutaneous lesions are not present, then viral isolation by culture is adequate for study entry but is not required. In the case of no cutaneous lesions and negative viral cultures, however, the CSF polymerase chain reaction (PCR) must be positive. Additional sites from which HSV culture will be attempted include conjunctivae, oropharynx, blood buffy coat, urine, and CSF. Evidence for central nervous system (CNS) HSV disease during the acute illness, including one or more of the following: Abnormal CSF indices for term infants: greater than 22 white blood cells (WBCs)/mm^3 and protein greater than 115mg/dl. Abnormal CSF indices for preterm infants: greater than 25 WBCs/mm^3 and protein greater than 220 mg/dl. Abnormal neuroimaging study (computed tomography [CT] with contrast, magnetic resonance imaging [MRI] with gadolinium, or head ultrasound) [NOTE: CT with contrast is the preferred imaging study]. Abnormal electroencephalography (EEG), if performed (NOTE: EEG is suggested for the evaluation of infants with HSV disease but is not required for this study]. Positive CSF PCR for HSV deoxyribonucleic acid (DNA) [NOTE: If no cutaneous lesions are present and all viral cultures are negative, the CSF PCR must be positive. If lesions are present and are culture-positive, abnormal CNS neurodiagnostic studies or abnormal CSF indices are sufficient for study entry]. Negative CSF PCR result within 48 hours prior to completion of intravenous acyclovir therapy. Less than or equal to 28 days of age at the time of initial presentation with CNS disease. Birth weight greater than or equal to 800 grams. Exclusion Criteria: Infants with either a grade 3 or grade 4 intraventricular hemorrhage (IHV) prior to study enrollment. Breast feeding infants whose mothers are taking acyclovir, valacyclovir, or famciclovir for greater than 120 hours (greater than 5 days). If at any point following enrollment the mother takes these antiviral drugs for greater than 120 hours (greater than 5 days), she will be asked to refrain from breast feeding while taking the drug. Infants known to be born to women who are human immunodeficiency virus (HIV) positive (but HIV testing is not required for study entry). These infants are at known risk of acquiring HIV, which would alter their immune response to other infections, including herpes simplex virus (HSV) infection. Additionally, they may be receiving antiretroviral and/or antiviral drugs during the time in which the study of suppressive oral acyclovir is being conducted. As such, they will be excluded if the mother's positive HIV status is known at the time of evaluation for study inclusion. If at any point following enrollment it is learned that an infant is HIV positive, however, he/she will be continued on the study protocol. Infants with HSV infection limited to the skin, eyes, or mouth (SEM). Patients with SEM HSV infection will be considered for enrollment and randomization in the ongoing Collaborative Antiviral Study Group (CASG) evaluation of oral suppressive acyclovir therapy following neonatal HSV infections limited to the SEM. Infants with creatinine greater than 1.5 mg/dl at time of study enrollment.

Oral suspension 300 mg/m^2/dose TID for 6 months.

Acyclovir

Nc1nc2c(ncn2COCCO)c(=O)[nH]1

D06BB03 | D06BB53 | J05AB01 | S01AD03

NCT00033917

NCT00033917_EG000

Accepts Healthy Volunteers

All

Child

Phase 3

Preterm infants < 1250 g birth weight Admitted to participating institution < 6 hrs of age No evidence for congenital malformations Cranial US at 6 postnatal hours without evidence of Grades III - IV intraventricular hemorrhage

Those subjects with no evidence for intraventricular hemorrhage (IVH) at 6 - 12 postnatal hours. These subjects were randomized to early low-dose indomethacin (0.1 mg/kg/d for 3 doses).

Indomethacin

COc1ccc2c(c1)c(CC(=O)O)c(C)n2C(=O)c1ccc(Cl)cc1

C01EB03 | M01AB01 | M01AB51 | M02AA23 | S01BC01 | S01CC02

NCT00040443

NCT00040443_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion criteria Clinical diagnosis of mild cognitive impairment Good general health with no additional diseases that would interfere with the study. Exclusion criteria Any significant neurologic disease (other than suspected incipient Alzheimer's disease), such as Parkinson's disease, stroke, TIA's, multi-infarct dementia, Huntington's disease, head trauma, chronic CNS infection. History of major depression or another major psychiatric disorder within the past 6 months. History of schizophrenia, mania or recurrent psychotic episodes. History of alcohol or DSM IV-diagnosed substance abuse or dependence disorder within the past year. History of blackout, epilepsy or seizures, or an abnormal EEG as judged by the Investigator and considering the age of the participant. Any clinically significant hepatic, renal, cardiovascular, pulmonary, gastrointestinal or hematological illness or unstable medical condition which could interfere with drug safety, or absorption, distribution, metabolism and excretion, or lead to difficulty complying with the protocol.

CX516 - 900 mg (3 X 300 mg) CX516 (Ampalex®)

CX516

O=C(c1ccc2nccnc2c1)N1CCCCC1

NCT00041392

NCT00041392_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Coronary heart disease Exclusion Criteria: Early dementia History of psychiatric illness

100 mg/kg magnesium

Magnesium

[MgH2]

NCT00041392

NCT00041392_EG001

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Coronary heart disease Exclusion Criteria: Early dementia History of psychiatric illness

100 mg/kg 0.9 % saline

SODIUM CHLORIDE

[Cl-].[Na+]

A12CA01 | B05CB01 | B05XA03 | S01XA03

NCT00045487

NCT00045487_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Patients must have histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma (RCC). Papillary RCC is permitted only if immunohistochemical evidence of strong (2-3+) EGFR expression. Disease that is recurrent or refractory to IL-2 or IFN-based therapy or new diagnosis in previously untreated patients who are not appropriate candidates to receive IL-2 -based treatment Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. Prior nephrectomy or resection of metastatic lesions permitted if full surgical recovery has occurred. Age > 18 years Because no dosing or adverse event data are currently available on the use of OSI-774 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable. Life expectancy of at least 12 weeks ECOG performance status of 0,1 or 2 or Karnofsky >60% Patients must have normal organ and marrow function as defined below: Hematopoietic Absolute neutrophil count at least ≥ 1,500/ul Platelet ≥ 100,000/uL Hemoglobin ≥ 9.0 g/dL, concomitant erythropoetin permitted Hepatic a. Total bilirubin within normal institutional limits b. AST (SGOT)/ALT (SGPT) ≤ 2.5 times institutional upper limit of normal (≤5 times ULN if liver metastases present) Renal a. Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance > 60 mL/min/1.73m2 Calcium a. Corrected calcium < 12.0 mg/dl, concomitant hypocalcemic agents permitted Complete supportive and palliative care will continue to be provided to ameliorate signs and symptoms that were pre-existing or may arise while on study and which do not interfere with the objectives of the study. The use of erythropoietin and biphosphonates is permitted. Patients must have tumor blocks available for EGFR expression analysis to be eligible for treatment on this study. Exclusion Criteria: History of active malignancy (other than RCC) in the past 3 years, other than nonmelanomatous skin cancer or in situ breast cancer or in situ cervical cancer. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774. Prior treatment with EGFR targeting therapies. Inability to understand the written informed consent document. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Major surgery, or significant traumatic injury occurring within 21 days prior to treatment. Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test). Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Pregnant women are excluded from this study because OSI-774 is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development. For this reason, women of childbearing potential and men must also agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with OSI-774. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Informed Consent - No study specific procedures will be performed without a written and signed informed consent document. Patients who do not demonstrate the ability to understand or the willingness to sign the written informed consent document are excluded from study entry.

Once-daily oral administration for 4 weeks.

Erlotinib

C#Cc1cccc(Nc2ncnc3cc(OCCOC)c(OCCOC)cc23)c1

L01EB02 | L01XE03

NCT00045734

NCT00045734_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Histologically confirmed meningioma Benign, malignant, or atypical disease Neurofibromatosis (NF) type 1 or 2 allowed Hemangiopericytoma allowed Unequivocal evidence of tumor recurrence or progression by MRI or CT scan (on steroid dosage that is stable for at least 5 days) Evaluable residual disease by MRI or CT scan if previously treated with surgical resection for recurrent or progressive disease Newly diagnosed recurrent disease that requires surgical debulking allowed Prior standard external-beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery allowed provided disease has progressed since completion of therapy Patients who have had prior brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon positron-emission tomography or thallium scanning, magnetic resonance spectroscopy, or surgical documentation Patients with a history of NF may have other stable Central Nervous System (CNS) tumors (e.g., schwannoma, acoustic neuroma, or ependymoma) provided those lesions have been stable in size for the past 6 months Performance status - Karnofsky 60-100% More than 8 weeks Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 120,000/mm^3 Hemoglobin at least 10 g/dL (transfusions allowed) No bleeding disorders Bilirubin less than 2 times upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) less than 2 times ULN Prothrombin Time (PT), Partial thromboplastin time (PTT), and International normalized Ratio (INR) no greater than 1.5 times ULN Creatinine less than 1.5 mg/dL Creatinine clearance at least 60 mL/min No deep venous or arterial thrombosis within the past 6 weeks No pulmonary embolism within the past 6 weeks No serious active infection No prior intracranial hemorrhage No concurrent disease that would obscure toxicity or dangerously alter drug metabolism No other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix unless the patient is in complete remission and off all therapy for that disease for at least 3 years No other significant medical illness that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after study participation At least 1 week since prior interferon or thalidomide No concurrent immunotherapy Concurrent epoetin alfa allowed At least 4 weeks since prior cytotoxic chemotherapy At least 2 weeks since prior vincristine At least 6 weeks since prior nitrosoureas At least 3 weeks since prior hydroxyurea or procarbazine No concurrent chemotherapy At least 1 week since prior tamoxifen No concurrent hormonal therapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Recovered from prior surgery Recovered from all prior therapy At least 1 week since prior noncytotoxic therapy (e.g., isotretinoin) except radiosensitizers At least 2 weeks since prior drugs that affect hepatic metabolism At least 4 weeks since prior investigational agents No concurrent warfarin (heparin or low-molecular weight heparin allowed) No other concurrent investigational agents No concurrent acetaminophen of more than 500 mg/day No other concurrent anticancer therapy

Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies

Imatinib

Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1

L01EA01 | L01XE01

NCT00047697

NCT00047697_EG000

No

All

Child

Phase 2

Inclusion Criteria: Autism Spectrum Disorder (ASD) Asperger's Disorder IQ of 75 or above Baseline assessment tests within the acceptable range Exclusion Criteria: Bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic disorder Seizure disorder requiring the use of anticonvulsant medications Congenital rubella, cytomegalovirus, or tuberous sclerosis Certain medications prescribed for management of behavior (please contact the investigator for a complete list) Medications/preparations that are known to interact with donepezil HCl Significant medical illness, endocrinopathies, cardiovascular disease, or severe chronic malnutrition Pregnancy or sexually active females not using a reliable method of contraception

5 mg of donepezil for 4 weeks, followed by 10 mg of donepezil for 6 weeks.

Donepezil

COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2

N06DA02 | N06DA52 | N06DA53

NCT00048815

NCT00048815_EG000

No

All

Adult | Older Adult

Not Applicable

Inclusion Criteria: Minor Depression symptoms for at least 6 months Endorse one of the DSM-IV "A" criteria for MDD and at least one other symptom of MDD or endorse both of the "A" criteria for MDD Global Assessment of Functioning (GAF) score < 70 Short form health survey (SF-36) social functioning score <= 75% or an emotional role functioning score <= 67% HAM-D-17 score 10-17, inclusive Minor depression symptoms for at least 6 months Exclusion Criteria: Major depressive disorder (MDD) or dysthymia within the past year or in partial remission of MDD At least a 12-week course of either citalopram at a minimum or 40 mg/day or St. John's Wort at a minimum of 900 mg/day during the current episode of depression Previous intolerance to either citalopram or St. John's Wort or history of nonresponse to either citalopram at a minimum of 40 mg/day or St. John's Wort at a minimum of 900 mg/day for at least 12 weeks Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease Uncontrolled seizure disorder The following DSM-IV diagnoses: organic mental disorders; substance use disorders, including alcohol, active within the last year or patients with a positive urine drug screen; schizophrenia; delusional disorder; psychotic disorders not elsewhere classified; bipolar disorder; bereavement; adjustment disorder; antisocial personality disorder; panic disorder, social phobia, generalized anxiety disorder (GAD), or obsessive compulsive disorder (OCD). Patients may have a lifetime diagnosis of an anxiety disorder as long as it is not current. Mood-congruent or mood-incongruent psychotic features Psychotropic drugs Hypothyroidism Investigational psychotropic drugs within the last year Positive toxicology screen Medications metabolized by the CYP3A4 system, where induction of this system poses a risk to the medical stability of the patient Pregnancy or refusal to use a medically accepted method of contraception Serious suicide or homicide risk Psychotherapy beginning less than 3 months ago

Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.

Citalopram

CN(C)CCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21

N06AB04 | N06AB10

NCT00048815

NCT00048815_EG001

No

All

Adult | Older Adult

Not Applicable

Inclusion Criteria: Minor Depression symptoms for at least 6 months Endorse one of the DSM-IV "A" criteria for MDD and at least one other symptom of MDD or endorse both of the "A" criteria for MDD Global Assessment of Functioning (GAF) score < 70 Short form health survey (SF-36) social functioning score <= 75% or an emotional role functioning score <= 67% HAM-D-17 score 10-17, inclusive Minor depression symptoms for at least 6 months Exclusion Criteria: Major depressive disorder (MDD) or dysthymia within the past year or in partial remission of MDD At least a 12-week course of either citalopram at a minimum or 40 mg/day or St. John's Wort at a minimum of 900 mg/day during the current episode of depression Previous intolerance to either citalopram or St. John's Wort or history of nonresponse to either citalopram at a minimum of 40 mg/day or St. John's Wort at a minimum of 900 mg/day for at least 12 weeks Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease Uncontrolled seizure disorder The following DSM-IV diagnoses: organic mental disorders; substance use disorders, including alcohol, active within the last year or patients with a positive urine drug screen; schizophrenia; delusional disorder; psychotic disorders not elsewhere classified; bipolar disorder; bereavement; adjustment disorder; antisocial personality disorder; panic disorder, social phobia, generalized anxiety disorder (GAD), or obsessive compulsive disorder (OCD). Patients may have a lifetime diagnosis of an anxiety disorder as long as it is not current. Mood-congruent or mood-incongruent psychotic features Psychotropic drugs Hypothyroidism Investigational psychotropic drugs within the last year Positive toxicology screen Medications metabolized by the CYP3A4 system, where induction of this system poses a risk to the medical stability of the patient Pregnancy or refusal to use a medically accepted method of contraception Serious suicide or homicide risk Psychotherapy beginning less than 3 months ago

Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.

Hypericum

CC1(C)SC2C(NC=O)C(=O)N2C1C(=O)O

NCT00050622

NCT00050622_EG002

No

All

Child

Not Applicable

Inclusion Criteria: Attention Deficit Hyperactivity Disorder IQ >= 80 Exclusion Criteria: History of seizures or other neurological problems Medical history that would involve considerable risk in taking stimulant medication History or concurrent diagnosis of any of the following disorders: pervasive developmental disorder, schizophrenia or other psychotic disorders, sexual disorder, organic mental disorder, or eating disorder

0.3 mg/kg MPH, No BMOD

Methylphenidate

COC(=O)C(c1ccccc1)C1CCCCN1

N06BA04 | N06BA11 | N06BA15

NCT00052442

NCT00052442_EG000

No

All

Adult | Older Adult

Phase 1 | Phase 2

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma or, using the World Health Organization (WHO) classification, aggressive non-Hodgkin's lymphoma including: Large B- or T-cell lymphomas (including transformed lymphomas) Mantle cell lymphoma Immunoblastic lymphoma At least 1 unidimensionally measurable lesion At least 2 centimeter (cm) by conventional techniques OR At least 1 cm by spiral computerized tomography (CT) scan Lymph nodes no greater than 1 cm in the short axis are considered normal Relapsed or refractory disease after first-line chemotherapy Cohort 1: No more than 3 prior conventional cytotoxic chemotherapy regimens Must have had at least a partial response (PR) lasting no more than 6 months or refractory disease Patients with disease refractory to or relapsed less than 100 days from peripheral blood stem cell (PBSC) transplantation are not eligible Cohort 2: No limit on prior treatment Must have had at least a PR to the last therapy lasting at least 6 months Patients who have received high-dose chemotherapy as part of peripheral blood stem cells (PBSC) transplantation are eligible if relapse occurred at least 100 days after transplantation No clinically significant pleural effusions or ascites No active brain or leptomeningeal metastases Treated Central nervous system (CNS) disease allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 75,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) Aspartate aminotransferase/alanine aminotransferase (AST/ALT) no greater than 2.5 times ULN (4 times ULN if liver involvement) Alkaline phosphatase no greater than 5 times ULN Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular No symptomatic congestive heart failure No New York Heart Association class III or IV heart disease No unstable angina pectoris No cardiac arrhythmia No myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months No history of orthostatic hypotension No ECG evidence of acute ischemia or significant conduction abnormality (e.g., bifascicular block or 2nd or 3rd degree atrioventricular blocks) No uncontrolled hypertension requiring active manipulation of antihypertensive medications No grade III or IV edema Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection Febrile episodes up to 38.5° Celsius without signs of active infection allowed No other concurrent active cancer No other concurrent serious medical illness No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 3 months since prior monoclonal antibody therapy (e.g., rituximab) Chemotherapy See Disease Characterisitics At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy At least 7 days since prior steroids No concurrent steroids Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Surgery More than 4 weeks since prior major surgery Other No prior antifolates No concurrent folic acid supplementation No other concurrent investigational agents No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy

Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.

Pralatrexate

C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

L01BA05

NCT00052442

NCT00052442_EG001

No

All

Adult | Older Adult

Phase 1 | Phase 2

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma or, using the World Health Organization (WHO) classification, aggressive non-Hodgkin's lymphoma including: Large B- or T-cell lymphomas (including transformed lymphomas) Mantle cell lymphoma Immunoblastic lymphoma At least 1 unidimensionally measurable lesion At least 2 centimeter (cm) by conventional techniques OR At least 1 cm by spiral computerized tomography (CT) scan Lymph nodes no greater than 1 cm in the short axis are considered normal Relapsed or refractory disease after first-line chemotherapy Cohort 1: No more than 3 prior conventional cytotoxic chemotherapy regimens Must have had at least a partial response (PR) lasting no more than 6 months or refractory disease Patients with disease refractory to or relapsed less than 100 days from peripheral blood stem cell (PBSC) transplantation are not eligible Cohort 2: No limit on prior treatment Must have had at least a PR to the last therapy lasting at least 6 months Patients who have received high-dose chemotherapy as part of peripheral blood stem cells (PBSC) transplantation are eligible if relapse occurred at least 100 days after transplantation No clinically significant pleural effusions or ascites No active brain or leptomeningeal metastases Treated Central nervous system (CNS) disease allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 75,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) Aspartate aminotransferase/alanine aminotransferase (AST/ALT) no greater than 2.5 times ULN (4 times ULN if liver involvement) Alkaline phosphatase no greater than 5 times ULN Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular No symptomatic congestive heart failure No New York Heart Association class III or IV heart disease No unstable angina pectoris No cardiac arrhythmia No myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months No history of orthostatic hypotension No ECG evidence of acute ischemia or significant conduction abnormality (e.g., bifascicular block or 2nd or 3rd degree atrioventricular blocks) No uncontrolled hypertension requiring active manipulation of antihypertensive medications No grade III or IV edema Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection Febrile episodes up to 38.5° Celsius without signs of active infection allowed No other concurrent active cancer No other concurrent serious medical illness No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 3 months since prior monoclonal antibody therapy (e.g., rituximab) Chemotherapy See Disease Characterisitics At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy At least 7 days since prior steroids No concurrent steroids Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Surgery More than 4 weeks since prior major surgery Other No prior antifolates No concurrent folic acid supplementation No other concurrent investigational agents No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy

Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.

Pralatrexate

C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

L01BA05

NCT00052442

NCT00052442_EG003

No

All

Adult | Older Adult

Phase 1 | Phase 2

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma or, using the World Health Organization (WHO) classification, aggressive non-Hodgkin's lymphoma including: Large B- or T-cell lymphomas (including transformed lymphomas) Mantle cell lymphoma Immunoblastic lymphoma At least 1 unidimensionally measurable lesion At least 2 centimeter (cm) by conventional techniques OR At least 1 cm by spiral computerized tomography (CT) scan Lymph nodes no greater than 1 cm in the short axis are considered normal Relapsed or refractory disease after first-line chemotherapy Cohort 1: No more than 3 prior conventional cytotoxic chemotherapy regimens Must have had at least a partial response (PR) lasting no more than 6 months or refractory disease Patients with disease refractory to or relapsed less than 100 days from peripheral blood stem cell (PBSC) transplantation are not eligible Cohort 2: No limit on prior treatment Must have had at least a PR to the last therapy lasting at least 6 months Patients who have received high-dose chemotherapy as part of peripheral blood stem cells (PBSC) transplantation are eligible if relapse occurred at least 100 days after transplantation No clinically significant pleural effusions or ascites No active brain or leptomeningeal metastases Treated Central nervous system (CNS) disease allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 75,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) Aspartate aminotransferase/alanine aminotransferase (AST/ALT) no greater than 2.5 times ULN (4 times ULN if liver involvement) Alkaline phosphatase no greater than 5 times ULN Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular No symptomatic congestive heart failure No New York Heart Association class III or IV heart disease No unstable angina pectoris No cardiac arrhythmia No myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months No history of orthostatic hypotension No ECG evidence of acute ischemia or significant conduction abnormality (e.g., bifascicular block or 2nd or 3rd degree atrioventricular blocks) No uncontrolled hypertension requiring active manipulation of antihypertensive medications No grade III or IV edema Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection Febrile episodes up to 38.5° Celsius without signs of active infection allowed No other concurrent active cancer No other concurrent serious medical illness No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 3 months since prior monoclonal antibody therapy (e.g., rituximab) Chemotherapy See Disease Characterisitics At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy At least 7 days since prior steroids No concurrent steroids Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Surgery More than 4 weeks since prior major surgery Other No prior antifolates No concurrent folic acid supplementation No other concurrent investigational agents No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy

Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.

Pralatrexate

C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

L01BA05