IDEC-C2B8 - RESULTS OF A PHASE-I MULTIPLE-DOSE TRIAL IN PATIENTS WITHRELAPSED NON-HODGKINS-LYMPHOMA

Purpose: To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD2O monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma. Patients and Met hods: Twenty patients with relapsed low-grade (n = 15) or intermediate -/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m(2) (n = 3), 250 mg/m(2) (n = 7), or 375 mg/m(2) (n = 10) of I DEC-C2B8. Results: Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urt icaria. More serious events were rare, Peripheral-blood B cells were r apidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels, Antibody serum half life (a nd maximum concentration [C-max]) generally increased between the firs t and fourth infusions (33.2 hours v 76.6 hours, respectively) followi ng the 375-mg/m(2) doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 month s (range, 3 to 21.7). Minor responses (MRs) were observed in five pati ents and progressive disease (PD) in seven, Tumor responses occurred i n peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and e xtranodal sites, and in patients who had relapsed following high dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded, Four of six with bulky disease had a PR. Conclusi on: IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375- mg/m(2) dose has been selected for a phase II trial in patients with r elapsed low-grade or follicular B-cell lymphoma. (C) 1997 by American Society of Clinical Oncology.