Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma
I. Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan
(IDEC-90Y2B8) administered with rituximab with and without filgrastim (G-CSF) and
interleukin-11 (IL-11) in patients with relapsed low-grade or follicular CD20+ non-Hodgkin's
lymphoma. (Phase I) II. Determine the toxicity of this regimen in these patients. III.
Determine the response rate in patients treated with this regimen. IV. Compare tumor and
normal organ dosimetry with positron emission tomography and computerized tomography scans,
subsequent tumor response, and normal organ toxicity by utilizing indium In 111 ibritumomab
tiuxetan radioimmunoconjugate scans before each IDEC-90Y2B8 dose in these patients. (Phase
I) V. Determine the immune response to this regimen, in terms of human anti-mouse and human
anti-chimeric antibody formation, in these patients. (Phase I) VI. Determine whether G-CSF
and IL-11 can ameliorate the effect of the MTD of IDEC-90Y2B8 on bone marrow function in
these patients. (Phase I) VII. Determine progression-free survival at 3 years. (Phase II)
PHASE I: Patients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan
IV over 10 minutes on day 1 (for radioimaging), and IDEC-90Y2B8 IV over 10 minutes on day 8.
Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease
progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) of IDEC-90Y2B8
is determined, patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning
when absolute neutrophil count is less than 1,500/mm3 and continuing until blood counts
recover. Patients also receive interleukin-11 (IL-11) SC beginning when platelet count is
less than 75,000/mm^3 and continuing until blood counts recover. Patients undergo PBSC
transplantation only if marrow recovery is inadequate.
Cohorts of 3-6 patients receive escalating doses of IDEC-90Y2B8 until the MTD is determined.
The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience
dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to
determine the MTD of this radioimmunotherapy with the addition of the prophylactic
cytokines, G-CSF and IL-11.
PHASE II: Patients receive rituximab, indium In 111 ibritumomab tiuxetan, and IDEC-90Y2B8 IV
as determined at the MTD in phase I. Treatment repeats 24-36 weeks later for a total of 2
courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 1 year, every
4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan (Phase I)
If at any time 2 or more patients (of a maximum of 6) at any dose level experience DLT, then the MTD will be defined as the previous dose level.
At 8 weeks
United States: Food and Drug Administration
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