A phase I study of 90yttrium-ibritumomab-tiuxetan in children and adolescents with relapsed/refractory CD20-positive non-Hodgkin's lymphoma: a Children's Oncology Group study.

PURPOSE: The prognosis for children with recurrent CD20+ non-Hodgkin's lymphoma is dismal. A radiolabeled anti-CD20 antibody, 90yttrium-ibritumomab-tiuxetan (90Y-IT), is Food and Drug Administration approved for adults with recurrent indolent CD20+ B cell-non-Hodgkin's lymphoma. There is no data on the safety and feasibility of 90Y-IT in refractory childhood CD20+ lymphoma.

EXPERIMENTAL DESIGN: Children and adolescents with refractory/relapsed CD20+ lymphoma were eligible for this phase I radioimmunotherapy study. Patients (n=5) received rituximab (250 mg/m2 i.v.) on days 0 and 7 and indium-111 ibritumomab-tiuxetan (5 mCi i.v.) on day 0. Dosimetry studies were done on days 0, 1, 3, and 6. Immediately after rituximab on day 7, patients received 90Y-IT if dosimetry studies showed<2000 cGy exposure to all solid organs and<300 cGy to marrow, as well as 0.4 mCi/kg in patients with good marrow reserve (n=3) and 0.1 mCi/kg in patients with poor marrow reserve (after bone marrow transplant; n=2).

RESULTS: No patients experienced nonhematologic or hematologic dose-limiting toxicity. Human antimurine antibody/human antichimeric antibody incidence was 0%. One patient experienced grade II infusion-related chills associated with rituximab. The following are the means of organ radiation exposure (cGy): kidneys 341 (112-515), liver 345 (83-798), lungs 309 (155-519), marrow 46 (20-78), spleen 565 (161-816), and total body 42 (14-68).

CONCLUSIONS: Based on these findings, an expanded investigator-initiated limited institutional phase II study has been designed to further evaluate the safety, tolerability, and response rate with 90Y-IT dose stratification based on marrow reserve.