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

Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5652s-5660s. doi: 10.1158/1078-0432.CCR-07-1060.

Abstract

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / immunology*
  • Bone Marrow / radiation effects
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / therapeutic use
  • Indium Radioisotopes
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Male
  • Neoplasm Recurrence, Local / radiotherapy*
  • Radiation Dosage
  • Radioimmunotherapy*
  • Radiotherapy Dosage
  • Rituximab
  • Tissue Distribution
  • Yttrium Radioisotopes / pharmacokinetics
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Immunoconjugates
  • Indium Radioisotopes
  • Yttrium Radioisotopes
  • Rituximab
  • ibritumomab tiuxetan