A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma.

Abstract

UNLABELLED:

Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo.

METHODS:

All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow.

RESULTS:

67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6: 1, respectively. This 67Cu-2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting.

CONCLUSION:

67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.

• Authors: R T O'Donnell, G L DeNardo, D L Kukis, K R Lamborn, S Shen, A Yuan, D S Goldstein, C E Carr, G R Mirick, S J DeNardo
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 40 Issue 12 Pg. 2014-20 (Dec 1999) ISSN: 0161-5505 [Print] United States
• PMID: 10616879 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Heterocyclic Compounds
• Organometallic Compounds
• copper-67-2IT-BAT-Lym-1

Topics

• Bone Marrow (radiation effects)
• Female
• Heterocyclic Compounds (adverse effects, therapeutic use)
• Humans
• Lymphoma, Non-Hodgkin (radiotherapy)
• Male
• Middle Aged
• Organometallic Compounds (adverse effects, therapeutic use)
• Radioimmunotherapy
• Radiotherapy Dosage