A Phase I Study Of Yttrium-Ibritumomab Tiuxetan (90Y Zevalin, Yttrium (90)-Anti-CD20, NSC # 710085) Preceded By Rituximab In Children With Recurrent/Refractory CD20 Positive Lymphoma
I. Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan
(IDEC-Y2B8) when preceded by rituximab in children with recurrent or refractory
CD20-positive lymphoma for which no autologous peripheral blood stem cell transplantation
(AuPBSCT) is planned. (Group A) If the dose-limiting toxicity (DLT) in group A is purely
hematological, determine the MTD of IDEC-Y2B8 when combined with rituximab, AuPBSCT, and
filgrastim (G-CSF) in a second group of children with recurrent or refractory CD20-positive
lymphoma. (Group B) II. Determine the DLT of rituximab and IDEC-Y2B8 in these patients. III.
Determine the dosimetry of indium In 111 ibritumomab tiuxetan preceded by rituximab in these
IV. Determine, preliminarily, the antitumor activity of rituximab and IDEC-Y2B8 in these
V. Assess the immune cell depletion (B-cell and T-cell) and recovery in patients treated
with this regimen.
VI. Determine the human anti-mouse antibody response in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan
(IDEC-Y2B8). Patients are assigned to 1 of 2 groups.
GROUP A (no planned peripheral blood stem cell [PBSC] support): Patients receive rituximab
IV over 4-6 hours followed by indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10
minutes on day 0 and undergo whole body imaging. Patients may then receive rituximab IV over
4-6 hours followed by IDEC-Y2B8 IV over 10 minutes on day 7.
Cohorts of 3-6 patients in each subgroup (A1, A2, and A3) receive escalating doses of
IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined (subgroup A1 closed as of
10/8/04). The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6
patients experience dose-limiting toxicity (DLT).
Some patients receive autologous PBSC IV over 30-60 minutes on day 35.
GROUP B (planned PBSC support): Patients receive rituximab, IDEC-In2B8, and IDEC-Y2B8 as in
group A. Patients also receive autologous PBSC IV over 30-60 minutes on day 21 and
filgrastim (G-CSF) subcutaneously beginning on day 22 and continuing until blood counts
recover or day 35.
If the DLT in group A is purely hematological, cohorts of 3-6 patients in group B receive
escalating doses of IDEC-Y2B8 until the MTD is determined. The MTD is defined as in group A.
Patients in both groups are followed at days 63, 90, 180, 365, and then annually thereafter.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD, defined as that dose at which fewer than one-third of patients experience DLT graded according to the NCI CTC v 2.0
Up to day 49
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|