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Methods and Findings in Experimental... Dec 2009[Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate,...
[Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib, Vorinostat.
Topics: Clinical Trials as Topic; Humans
PubMed: 20140276
DOI: No ID Found -
Haematologica May 2010This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced... (Comparative Study)
Comparative Study
This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid pre-medication). An initial dose of 4 mg/kg dacetuzumab exceeded the maximum-tolerated dose for uniform weekly dosing. Intrapatient dose escalation with steroid pre-medication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. Adverse events potentially related to dacetuzumab included cytokine release syndrome symptoms, non-infectious ocular inflammation, and elevated hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing. Clinical trials gov identifier: NCT00079716.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CD40 Antigens; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Inflammation; Male; Middle Aged; Multiple Myeloma
PubMed: 20133895
DOI: 10.3324/haematol.2009.008003 -
Leukemia & Lymphoma Feb 2010Despite advances in therapy, chronic lymphocytic leukemia remains an incurable disease and novel, effective therapies are needed. In this open-label, dose-escalation,...
Despite advances in therapy, chronic lymphocytic leukemia remains an incurable disease and novel, effective therapies are needed. In this open-label, dose-escalation, phase I study, dacetuzumab (IgG1 humanized monoclonal antibody) was administered to 12 adults, all of whom had received several prior systemic therapies (median, 4; range, 2-11). Intrapatient dose escalation (maximum weekly doses of 3-8 mg/kg) was used to diminish first-dose-related inflammatory symptoms. No dose-limiting toxicities or dose-dependent trends in adverse events (AEs) were observed. The most common AEs (in >/=2 patients) were fatigue, headache, anorexia, conjunctivitis, hyperhidrosis, and night sweats, all of which were mild or moderate. No deaths, serious AEs, or discontinuations due to AEs occurred. Although no patient achieved an objective response, five patients demonstrated stable disease after 1 cycle of therapy, with no discernable correlation between dacetuzumab dose and outcome. This modest single-agent activity may warrant further testing of dacetuzumab in combination with other chronic lymphocytic leukemia therapies.
Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Conjunctivitis; Dose-Response Relationship, Drug; Fatigue; Female; Headache; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Treatment Outcome
PubMed: 20038235
DOI: 10.3109/10428190903440946 -
Journal of Clinical Oncology : Official... Sep 2009To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell...
PURPOSE
To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL).
PATIENTS AND METHODS
In this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle.
RESULTS
In the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in >or= 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade >or= 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients.
CONCLUSION
Dacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.
Topics: Adult; Aged; Aged, 80 and over; Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CD40 Antigens; Cohort Studies; Cytokines; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fatigue; Female; Fever; Headache; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Recurrence; Treatment Outcome; Young Adult
PubMed: 19636010
DOI: 10.1200/JCO.2008.21.3017 -
Current Opinion in Investigational... Jun 2009Dacetuzumab, a humanized mAb targeting the CD40 antigen, is in development by Seattle Genetics Inc and licensee Genentech Inc for the potential treatment of...
Dacetuzumab, a humanized mAb targeting the CD40 antigen, is in development by Seattle Genetics Inc and licensee Genentech Inc for the potential treatment of hematological malignancies. The CD40 antigen is a highly expressed cell surface transmembrane protein that is present in normal B-cells. Experiments using blocking antibodies for the CD40 ligand demonstrated that CD40 signaling may play a role in the development and maintenance of B-cell hematological malignancies and some solid tumors. In vitro, dacetuzumab exhibited antitumor activity against several B-cell lymphoma and multiple myeloma (MM) cell lines, and induced direct apoptosis as well as the engagement of effective antibody-dependent cell-mediated cytotoxicity. In vivo, dacetuzumab demonstrated enhanced antitumor efficacy in combination with other mAbs and chemotherapeutic agents; many of these combinations are now being tested clinically. Early clinical trials have evaluated the pharmacokinetics, safety and efficacy of dacetuzumab monotherapy in patients with relapsed/refractory B-cell lymphomas or MM. Targeting CD40 with dacetuzumab resulted in modest antitumor activity in B-cell lymphomas and, to a lesser extent, in MM. In particular, patients with diffuse large B-cell lymphoma responded well to dacetuzumab; the drug is being pursued for this indication in phase II trials.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; CD40 Antigens; Cell Line, Tumor; Cell Proliferation; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Evaluation, Preclinical; Hematologic Neoplasms; Humans; Lymphoma, B-Cell; Macaca fascicularis; Mice; Multiple Myeloma; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 19513947
DOI: No ID Found -
Methods and Findings in Experimental... 2009(-)-Gossypol; Alemtuzumab, Amlodipine, Anakinra, Azacitidine; Bazedoxifene acetate, Belinostat, Bevacizumab, BI-201335, BI-2536, Biphasic insulin aspart, Bortezomib;...
(-)-Gossypol; Alemtuzumab, Amlodipine, Anakinra, Azacitidine; Bazedoxifene acetate, Belinostat, Bevacizumab, BI-201335, BI-2536, Biphasic insulin aspart, Bortezomib; Cetuximab, CNTO-328, Custirsen sodium; Dacetuzumab; Elacytarabine, Erlotinib hydrochloride, Everolimus, Exenatide; Forodesine hydrochloride, Fostamatinib disodium, Frovatriptan; Ibutamoren mesilate, Imatinib mesylate, IMC-18F1, INCB-18424, Indacaterol, Insulin detemir, Insulin glargine, Insulin glulisine; KW-0761, KW-2449; Lapatinib ditosylate, Liraglutide; MK-2461, Mycophenolic acid sodium salt; Peginterferon alfa-2a, Pemetrexed disodium, Pioglitazone hydrochloride/metformin hydrochloride, Pregabalin; rBCG-30; Satraplatin, SB-743921, Short ragweed pollen allergenic extract, SNS-314, Sorafenib, Sugammadex sodium, Sunitinib malate; Teriparatide; Valsartan/amlodipine besylate, Vinflunine, Vorinostat.
Topics: Clinical Trials as Topic; Humans
PubMed: 19357798
DOI: No ID Found -
Current Hematologic Malignancy Reports Oct 2008The treatment of non-Hodgkin lymphoma (NHL) has changed dramatically since the introduction of rituximab, a monoclonal antibody that binds to the B-cell transmembrane... (Review)
Review
The treatment of non-Hodgkin lymphoma (NHL) has changed dramatically since the introduction of rituximab, a monoclonal antibody that binds to the B-cell transmembrane protein CD20 and causes lysis of the lymphoma cells. Since then, a number of additional antibodies have been tested against other B-cell targets, resulting in variable efficacies. The goal of these newer agents is to achieve similar or better response rates as seen with rituximab and perhaps demonstrate activity in rituximab-refractory disease. Several of the antibodies have been investigated in combination with each other as well as with conventional chemotherapeutic regimens. Approval of such antibodies by regulatory committees and their eventual integration into clinical practice will likely depend on positive results from randomized trials.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Clinical Trials as Topic; Humans; Lymphoma, B-Cell; Rituximab
PubMed: 20425465
DOI: 10.1007/s11899-008-0027-5