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- Klinische proef NCT00098254
BAY 43-9006 (Sorafenib) to Treat Relapsed Non-Small Cell Lung Cancer
Phase II Study of Bay 43-9006 (Sorafenib) With Evaluation of RAS Signal Pathway in Patients With Relapsed Non-Small Cell Lung Cancer
This study will investigate the effects and side effects of BAY 43-9006 in patients with advanced, recurrent, or refractory non-small cell lung cancer (NSCLC). BAY 43-9006 is one of a new class of anticancer agents known as bi-aryl ureas.
Patients 18 years of age and older with NSCLC that has recurred or progressed after one regimen of chemotherapy may be eligible for this study. Candidates are screened with a medical history and physical examination; blood tests; tumor biopsy (see below); chest x-ray; electrocardiogram; and imaging studies, including positron emission tomography-computed tomography (PET-CT, see below) and dynamic, contrast-enhanced MRI (DCE-MRI, see below).
Participants take BAY 43-9006 by mouth twice a day, morning and evening. On the first and 15th days of treatment, patients are admitted to the hospital for pharmacokinetic studies; that is, a test of how the body handles the drug. For the test, blood is collected at intervals (at 15 minutes, 30 minutes, and 1, 2, 4, 6, 8, 12 and 24 hours after ingestion) to determine the drug's level in the bloodstream. Treatment with BAY 43-9006 continues until the study doctor determines that the medication is not beneficial or the patient wishes to withdraw from the study.
In addition to drug therapy, patients undergo the following tests and procedures:
- Physical examination every 4 weeks
- Blood pressure checks once a week during the first 4 weeks
- Blood tests every week
- CT scans or other imaging tests, such as ultrasound or MRI, every 8 weeks to evaluate the tumor's response to treatment. CT is an x-ray test that provides detailed pictures of the inside of the body. It can be done from different angles, providing a 3-dimensional picture of the part of the body being studied and allowing the doctor to see the location, nature, and extent of disease. MRI uses a powerful magnet and radio waves instead of x-rays to produce accurate, detailed pictures of organs and tissues.
- PET-CT approximately every 8 weeks to look at how different parts of the body take up and use glucose (a sugar nutrient). Because rapidly growing cells, such as tumors, use more sugar than normal cells do, this test can be used to detect cancer. For the test, the patient is given an injection of a sugar solution in which a radioactive tracer has been attached to the sugar molecule. A special camera detects the radiation emitted by the solution, and the resulting images show how much sugar is being used in various parts of the body. PET-CT uses the PET scan in combination with standard CT in a machine that does both tests.
- DCE-MRI after 2 weeks of treatment. This test uses MRI with a special non-radioactive dye to examine blood flow in a certain part of the body.
- Tumor biopsy (optional) after 2 weeks of treatment. A biopsy is the surgical removal of a small piece of tissue. The tumor biopsy is done either using a small bore needle under CT guidance or by direct visualization using a laparoscope/thoracoscope. For the needle biopsy, a needle is inserted through the skin and guided by CT into the tumor mass. For the laparoscopy/thoracoscopy, the patient is sedated or asleep and small lighted tubes are inserted into small holes made in the skin. The tumor is located and tissue withdrawn.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Maryland
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Bethesda, Maryland, Verenigde Staten, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
- INCLUSION CRITERIA:
Histologically documented Non-small cell lung cancer and confirmed by the Laboratory of Pathology at the Clinical Center/National Institutes of Health (NIH) or the Laboratory of Pathology at National Naval Medical Center (NNMC).
Recurrent or progressed Non-Small Cell Lung Cancer (NSCLC).
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 greater than 20 mm with conventional techniques or as greater than 10 mm with spiral Computed tomography (CT) scan.
Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by Common Terminology Criteria for Adverse Events (CTCAE) 3.0) and must not have had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior radiation or major surgery.
Age greater than 18 years (males or non-pregnant females). Because no dosing or adverse event data are currently available on the use of BAY 43-9006 in patients less than 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 greater than 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Karnofsky > 60%).
Patients must have adequate organ and marrow function (as defined below). Patients must have returned to base line or grade one from any acute toxicity related to prior therapy.
Leukocytes greater than 3,000/micro l;
Absolute neutrophil count greater than 1,200/micro l;
Platelets greater than 100,000/micro l;
International normalized ratio (INR) less than or equal to 1.2
Partial thromboplastin time (PTT) less than or equal to 36 seconds or abnormality can be explained by the presences of lupus anticoagulant
Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal;
Aspartate aminotransferase, oxaloacetic transaminase (AST,SGOT) and alanine transaminase, serum glutamic pyruvic transaminase (ALT,SGPT) less than 2.5 times the institutional upper limits of normal;
Creatinine or creatinine clearance less than or equal to 1.5 times the institutional upper limits of normal or greater than 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because kinase inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and continue for at least 2 months after completion. 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 BAY 43-9006, breastfeeding should be discontinued if the mother is treated with BAY 43-9006.
Ability to comply with daily oral self administration schedule, and the ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Patients with symptomatic brain metastases should 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. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Human immunodeficiency virus (HIV)positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that BAY 43-9006 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to BAY 43-9006.
Patients may not be receiving any other investigational agents.
History of another invasive malignancy in the last five years. Non-invasive, non-melanoma skin cancers will be allowed.
Patients with conditions that would impair their ability to swallow tablets are excluded.
Patients must not have any evidence of bleeding diathesis.
Patients must not be on therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for prothrombin time (PT), international normalized ratio (INR) or partial thromboplastin time (PTT) are met.
Both men and women and members of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit women and minorities in this study.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: BAY 43-9006 (Sorafenib)
Self administered oral doses at 400 mg twice a day with 250 ml (8 oz.) of water each morning and evening (i.e., 12-hourly) continuously in a 28 day cycle.
Tablets may be taken with or without food.
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Self administered oral doses at 400 mg twice a day with 250 ml (8 oz.) of water each morning and evening (i.e., 12-hourly) continuously in a 28 day cycle.
Tablets may be taken with or without food.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Response Rate
Tijdsspanne: 17 months
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Percentage of participants with response rate = CR + PR.
Response will be evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
CR (complete response) is the disappearance of all target lesions; PR (partial response) is a 30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease) is a 20% increase in the sum of the longest diameter of target lesions; and SD (stable disease) are small changes that do not meet the above criteria.
Please see the Protocol Link module for additional information about RECIST if desired.
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17 months
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Progression Free Survival
Tijdsspanne: 17 months
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Time between the first day of treatment to the day of disease progression. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions. Appearance of one or more new lesions and/or unequivocal progressions of existing non-target lesions. |
17 months
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The Number of Participants With Adverse Events
Tijdsspanne: 5 1/2 years
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Here are the total number of participants with adverse events.
For the detailed list of adverse events see the adverse event module.
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5 1/2 years
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Overall Survival
Tijdsspanne: 17 months
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Time between the first day of treatment to the days of death.
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17 months
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Percent of Participants With Genotyping of CYP3A4/5 and 5 Polymorphisms
Tijdsspanne: 58 months
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All patients will be genotyped for CYP3A4/5 and 5 polymorphisms.
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58 months
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Overall Survival Reported Separately for Participants With a Change in PLGF Below 11 pg/ml and Above 12 pg/ml
Tijdsspanne: 17 months
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Difference in placental derived growth factor (PLGF) between day 28 and day 0 of < 11 pg/ml vs. > 12 pg/ml.
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17 months
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Cytokine Levels
Tijdsspanne: 54 days
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Serial plasma samples were collected from all patients and cytokine levels were measured.
The concentrations of the cytokines were determined with recombinant standards and expressed as picograms per milliliter (pg/ml).
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54 days
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Correlation of Response to Treatment With KRAS Mutational Status
Tijdsspanne: 42 months
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Mutational analysis of these genes was performed on paraffin-imbedded tissue blocks from prior pathologic specimens.
Disease control rate was correlated with KRAS mutational status.
Disease control rate was defined as complete remission (CR) + partial remission (PR)+ stable disease (SD).
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42 months
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Overall Survival Associated With Basic Fibroblast Growth Factor (bFGF)
Tijdsspanne: 42 months
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Serum plasma is collected at the beginning of each cycle during the course of the study and analyzed by the enzyme-linked immunosorbent assay (ELISA).
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42 months
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Progression Free Survival Associated With Basic Fibroblast Growth Factor (bFGF)
Tijdsspanne: 17 months
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Serum plasma is collected at the beginning of each cycle during the course of the study and analyzed by the enzyme-linked immunosorbent assay (ELISA).
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17 months
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Percentage of Participants With an Increase or Decrease in the Reverse Contrast Transfer Rate (Kep), Forward Contrast Transfer Rate (Ktrans), and Extravascular Fraction (Ve) With the Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)
Tijdsspanne: 59 months
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DCE-MRI was used to evaluate changes (e.g.
decrease/increase in Ve, Ktrans, Kep value) in vascularity and quality of index lesions to provide early indication of treatment effect before changes in size can be perceived on CT.
Changes were reflected in a decrease/increase of Ve, Ktrans, or Kep (Kep, Ve, Ktrans measurements at day 0, day 14 and the difference between the day 14 and the day 0 measurements (day 14-day 0).
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59 months
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Percent of Participants Who Had Immunohistochemical Analysis Performed for Raf, MEK, ERK, ERK-1 and p90RSK,ERK, E Twenty-six (ETS)-Like Transcription Factor 1 (ELK-1) and p90Ribosomal S6 Kinase (p90RSK).
Tijdsspanne: 59 months
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Immunohistochemical analysis performed by using state specific antibodies against Raf, methyl ethyl ketone (MEK), extracellular-signal regulated kinase (ERK), and two downstream substrates of ERK, E twenty-six (ETS)-like transcription factor 1 (ELK-1) and p90Ribosomal S6 kinase (p90RSK).
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59 months
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Percent of Participants Who Had Cytokine Profiling for IL-6 and IL-8
Tijdsspanne: 60 months
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Serial plasma samples were collected from all patients at pretreatment (baseline - day 0), and on days 14, 28, and 54.
The concentrations of the cytokines were determined with recombinant standards and expressed as picograms per milliliter (pg/ml).
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60 months
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Percentage of Participants With BRAF Mutations
Tijdsspanne: 60 months
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Extracted DNA was subjected to an initial PCR using a single primer set encompassing codom V600.
Pyrosequencing was carried out on a Qiagen PyroMaark Q24 system.
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60 months
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Percent of Pts With Primary Pharmacoproteomic Modulation Targets
Tijdsspanne: 60 months
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Pharmacoproteomic modulation targets (AKT, p-AKT, ERK 1/2, MEK, Cyclin D, p-ERK 1/2, p-MEK, pMEK, eNOA, p-eNOA, Cleaved PARP, PDGFRbeta, p-PDGFRbeta,Cyclin D, CD31, PARP.
Caspase 9, Caspase 3, Cleaved Caspase-9 Cleaved Caspase 3)
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60 months
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Secondary Pharmacoproteomic Modulation Targets
Tijdsspanne: 60 months
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Secondary pharmacoproteomic modulation targets (mTOR, EGFR, Src, NFkB, STAT1, TGFa, p38, Jak 1, lkB, IGFR, p-mTOR, p-EGFR, p-Src, p-NFkB, p-STAT1, Phospho-p38, p-Jak1, p-lkB,Pyk2, p-Pyk2, VEGFR-2, GSK3beta, p-GSK3beta, p-bad, p-Bcl-2, PCNA, Fos, Raf, CREB, Rho, avbeta3complex, Bad, CD34, VEGFR-1, bfGF, vWF, Factor VIII, Annexin V, Bcl-2).
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60 months
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Giuseppe Giaccone, M.D., Ph.D., National Cancer Institute (NCI)
Publicaties en nuttige links
Algemene publicaties
- Choy H, Devore RF 3rd, Hande KR, Porter LL, Rosenblatt P, Yunus F, Schlabach L, Smith C, Shyr Y, Johnson DH. A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study). Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):931-7. doi: 10.1016/s0360-3016(00)00420-x.
- Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.
- Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. doi: 10.1200/JCO.2002.02.068.
- Kelly RJ, Rajan A, Force J, Lopez-Chavez A, Keen C, Cao L, Yu Y, Choyke P, Turkbey B, Raffeld M, Xi L, Steinberg SM, Wright JJ, Kummar S, Gutierrez M, Giaccone G. Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Clin Cancer Res. 2011 Mar 1;17(5):1190-9. doi: 10.1158/1078-0432.CCR-10-2331. Epub 2011 Jan 11.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van de luchtwegen
- Neoplasmata
- Longziekten
- Neoplasmata per site
- Neoplasmata van de luchtwegen
- Thoracale neoplasmata
- Carcinoom, bronchogeen
- Bronchiale neoplasmata
- Longneoplasmata
- Carcinoom, niet-kleincellige long
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Sorafenib
Andere studie-ID-nummers
- 050049
- 05-C-0049
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Niet-kleincellig longcarcinoom
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National Cancer Centre, SingaporeBeëindigdExtranodaal NK-T-CELL LYMFOMASingapore
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Adelphi Values LLCBlueprint Medicines CorporationVoltooidMastcelleukemie (MCL) | Agressieve systemische mastocytose (ASM) | SM w Assoc Clonal Hema Non-Mast Cell Lineage Disease (SM-AHNMD) | Smeulende systemische mastocytose (SSM) | Indolente systemische mastocytose (ISM) ISM-subgroep volledig gerekruteerdVerenigde Staten
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University of Alabama at BirminghamBeëindigdAnaplastisch grootcellig lymfoom | Angioimmunoblastisch T-cellymfoom | Perifere T-cellymfomen | Volwassen T-celleukemie | Volwassen T-cellymfoom | Perifeer T-cellymfoom niet gespecificeerd | T/Null Cell Systemisch Type | Cutaan t-cellymfoom met nodale / viscerale ziekteVerenigde Staten
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Masonic Cancer Center, University of MinnesotaWervingLymfoom | Folliculair lymfoom | Acute myeloïde leukemie | Multipel myeloom | Myelofibrose | Juveniele myelomonocytaire leukemie | Burkitt lymfoom | Acute lymfatische leukemie | Lymfoblastisch lymfoom | Chronische lymfatische leukemie | Lymfoplasmacytisch lymfoom | Acute leukemie | Mantelcellymfoom | Chronische myelogene... en andere voorwaardenVerenigde Staten
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Roswell Park Cancer InstituteActief, niet wervendAcute myeloïde leukemie | Polycytemie Vera | Myelofibrose | Chronische myelomonocytische leukemie | Waldenström Macroglobulinemie | Acute lymfatische leukemie | Chronische lymfatische leukemie | Secundaire acute myeloïde leukemie | Sikkelcelziekte | Myelodysplastisch syndroom | Plasmacelmyeloom | Chronische... en andere voorwaardenVerenigde Staten
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Masonic Cancer Center, University of MinnesotaBeëindigdFolliculair lymfoom | Myelodysplastische syndromen | Multipel myeloom | Hodgkin lymfoom | Burkitt lymfoom | Acute lymfatische leukemie | Chronische lymfatische leukemie | Lymfoplasmacytisch lymfoom | Acute myeloïde leukemie | Mantelcellymfoom | Chronische myelogene leukemie | Prolymfatische Leukemie | Klein lymfocytisch... en andere voorwaardenVerenigde Staten
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Masonic Cancer Center, University of MinnesotaActief, niet wervendFolliculair lymfoom | Acute myeloïde leukemie | Multipel myeloom | Hodgkin lymfoom | Lymfoplasmacytisch lymfoom | Acute leukemie | Myelodysplastisch syndroom | Chronische myelogene leukemie | Prolymfatische Leukemie | Plasmacelleukemie | Beenmergfalensyndromen | Burkitt-lymfoom | Acute lymfoblastische leukemie... en andere voorwaardenVerenigde Staten
Klinische onderzoeken op BAY 43-9006 (Sorafenib)
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National Cancer Institute (NCI)VoltooidAcute myeloïde leukemie met FLT3/ITD-mutatieVerenigde Staten
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National Cancer Institute (NCI)BeëindigdRefractaire chronische lymfatische leukemie | Stadium I chronische lymfatische leukemie | Stadium II chronische lymfatische leukemie | Stadium III chronische lymfatische leukemie | Stadium IV chronische lymfatische leukemieVerenigde Staten
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National Cancer Institute (NCI)VoltooidRecidiverend diffuus grootcellig lymfoom bij volwassenen | Terugkerend volwassen immunoblastisch grootcellig lymfoom | Perifeer T-cellymfoom | Anaplastisch grootcellig lymfoom | Angioimmunoblastisch T-cellymfoom | Hepatosplenisch T-cellymfoom | Terugkerende T-celleukemie/lymfoom bij volwassenen | Recidiverend cutaan T-cel non-Hodgkin-lymfoomVerenigde Staten
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