{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:34:17Z","timestamp":1791092057064,"version":"4.1.0"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:p>PURPOSE: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation.<\/jats:p><jats:p>PATIENTS AND METHODS: Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin\u2019s lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression.<\/jats:p><jats:p>RESULTS: Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg\/kg\/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg\/kg\/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 \u00b1 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL). For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient was taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biospy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which was sustained in four patients through four courses.<\/jats:p><jats:p>CONCLUSION: The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.<\/jats:p>","DOI":"10.1200\/jco.2001.19.13.3280","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T07:26:22Z","timestamp":1487921182000},"page":"3280-3287","source":"Crossref","is-referenced-by-count":187,"title":["Phase I Study of Recombinant Human CD40 Ligand in Cancer Patients"],"prefix":"10.1200","volume":"19","author":[{"given":"Robert H.","family":"Vonderheide","sequence":"first","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice P.","family":"Dutcher","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Gail","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine F.","family":"Stephans","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Razvillas","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Garl","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Butine","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki P.","family":"Perry","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Armitage","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ghalie","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania A.","family":"Caron","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Gribben","sequence":"additional","affiliation":[{"name":"From the Department of Adult Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women\u2019s Hospital; and Harvard Medical School, Boston, MA; Cancer Center, Our Lady of Mercy Hospital, New York Medical College, Bronx, NY; Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX; and Immunex Corp, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1-091096","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.004313"},{"key":"R2-091096","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01340-1"},{"key":"R3-091096","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)90130-7"},{"key":"R4-091096","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03521.x"},{"key":"R5-091096","unstructured":"Vestal RE, Wingett DG, Knight LK, et al: Expression of CD40 in breast, colon, lung, and ovarian tumors. Proc Am Assoc Cancer Res 38: 230,1997 (abstr 1550)"},{"key":"R6-091096","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.18.8200"},{"key":"R7-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.1.1"},{"key":"R8-091096","doi-asserted-by":"publisher","DOI":"10.1038\/353678a0"},{"key":"R9-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.6.1543"},{"key":"R10-091096","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119822"},{"key":"R11-091096","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80078-7"},{"key":"R12-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.2.669"},{"key":"R13-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.4.1263"},{"key":"R14-091096","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4342"},{"key":"R15-091096","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.58.2.209"},{"key":"R16-091096","doi-asserted-by":"publisher","DOI":"10.1038\/357080a0"},{"key":"R17-091096","doi-asserted-by":"publisher","DOI":"10.1038\/35393"},{"key":"R18-091096","doi-asserted-by":"publisher","DOI":"10.1126\/science.7679801"},{"key":"R19-091096","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.111"},{"key":"R20-091096","doi-asserted-by":"publisher","DOI":"10.1126\/science.1702555"},{"key":"R21-091096","doi-asserted-by":"publisher","DOI":"10.1038\/30989"},{"key":"R22-091096","doi-asserted-by":"publisher","DOI":"10.1038\/30996"},{"key":"R23-091096","doi-asserted-by":"publisher","DOI":"10.1038\/31002"},{"key":"R24-091096","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.418"},{"key":"R25-091096","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.10.2787.2787"},{"key":"R26-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.1.159"},{"key":"R27-091096","unstructured":"Eliopoulos AG, Dawson CW, Mosialos G, et al: CD40-induced growth inhibition in epithelial cells is mimicked by Epstein-Barr Virus-encoded LMP1: Involvement of TRAF3 as a common mediator. Oncogene 13: 2243,1996-2254,"},{"key":"R28-091096","unstructured":"Murphy WJ, Asai O, Hirano A, et al: Inhibition of aggressive histology human B cell lymphoma growth by CD40 stimulation in vivo: A comparison of a CD40 antibody and a recombinant soluble CD40 ligand (srCD40L). Blood 88S: 89a,1996 (abstr 343)"},{"key":"R29-091096","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.15.5503-5515.2000"},{"key":"R30-091096","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.2999"},{"key":"R31-091096","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006012607452"},{"key":"R32-091096","unstructured":"Degli-Eposti MA, Klinke R, Armitage RJ, et al: CD40 ligand, a potent growth factor, causes apoptosis of bladder carcinoma cell lines. Blood 86S: 318a,1995 (abstr 1261)"},{"key":"R33-091096","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.10.3806"},{"key":"R34-091096","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.2.549"},{"key":"R35-091096","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1472"},{"key":"R36-091096","unstructured":"Fisher DC, Van den Abbeele A, Singer S, et al: Phase I trial with CD40-activated follicular lymphoma cells: A novel cellular vaccine strategy for B cell malignancies. Blood 92S: 247a,1998 (abstr 1010)"},{"key":"R37-091096","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.2917"},{"key":"R38-091096","doi-asserted-by":"crossref","unstructured":"Armitage RJ, Macduff BM, Spriggs MK, et al: Human B cell proliferation and Ig secretion induced by recombinant CD40 ligand are modulated by soluble cytokines. J Immunol 150: 3671,1993-3680,","DOI":"10.4049\/jimmunol.150.9.3671"},{"key":"R39-091096","doi-asserted-by":"publisher","DOI":"10.1038\/8426"},{"key":"R40-091096","doi-asserted-by":"publisher","DOI":"10.1038\/10495"},{"key":"R41-091096","doi-asserted-by":"publisher","DOI":"10.1038\/10503"},{"key":"R42-091096","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.2.441"},{"key":"R43-091096","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2000.40040393.x"},{"key":"R44-091096","doi-asserted-by":"crossref","unstructured":"Borges L, Miller RE, Jones J, et al: Synergistic action of fms-like tyrosine kinase 3 ligand and CD40 ligand in the induction of dendritic cells and generation of antitumor immunity in vivo. J Immunol 163: 1289,1999-1297,","DOI":"10.4049\/jimmunol.163.3.1289"},{"key":"R45-091096","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1994.1035"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2001.19.13.3280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T10:29:24Z","timestamp":1692700164000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2001.19.13.3280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7,1]]},"references-count":45,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2001,7,1]]}},"alternative-id":["10.1200\/JCO.2001.19.13.3280"],"URL":"https:\/\/doi.org\/10.1200\/jco.2001.19.13.3280","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,7,1]]}}}