Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma Journal Article

Authors: Czuczman, M. S.; Straus, D. J.; Divgi, C. R.; Graham, M.; Garin-Chesa, P.; Finn, R.; Myers, J.; Old, L. J.; Larson, S. M.; Scheinberg, D. A.
Article Title: Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma
Abstract: Purpose: Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. Methods: Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole- body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. Results: Median plasma and whole-body half-lives (T 1/2 ) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid- stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. Conclusion: Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.
Keywords: adult; clinical article; aged; unclassified drug; dose response; blood toxicity; antineoplastic activity; drug effect; monoclonal antibody; nonhodgkin lymphoma; iodine 131; isotope labeling; dosimetry; imaging; phase 1 clinical trial; drug half life; drug tolerance; intravenous drug administration; human; male; female; priority journal; article; okb 7
Journal Title: Journal of Clinical Oncology
Volume: 11
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1993-10-01
Start Page: 2021
End Page: 2029
Language: English
DOI: 10.1200/jco.1993.11.10.2021
PUBMED: 8410126
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Chaitanya Divgi
    127 Divgi
  2. Ronald D Finn
    252 Finn
  3. Steven M Larson
    779 Larson
  4. David J Straus
    213 Straus
  5. Lloyd J Old
    386 Old
  6. Martin C Graham
    29 Graham
  7. Jane E Myers
    10 Myers