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.
OBJECTIVE
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.


METHODS
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.
Cooney-Qualter
Erin
E
Division of Pediatric Heamtology and Blood and Marrow Transplantation, Medicine and Pathology, Columbia University, New York, New York 10032, and Children's Hospital of Philadelphia, PA, USA.
Krailo
Mark
M
Angiolillo
Anne
A
Fawwaz
Rashid A
RA
Wiseman
Gregory
G
Harrison
Lauren
L
Kohl
Virginia
V
Adamson
Peter C
PC
Ayello
Janet
J
vande Ven
Carmella
C
Perkins
Sherrie L
SL
Cairo
Mitchell S
MS
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D001853:Bone Marrow / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use; D007205:Indium Radioisotopes; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D011829:Radiation Dosage; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D000069283:Rituximab; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan