Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma
Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma
Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibody therapy and rituximab with and without filgrastim and interleukin-11 in treating patients who have relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal antibodies can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Biological therapies such as filgrastim and interleukin-11 use different ways to stimulate the immune system and stop cancer cells from growing.
PRIMARY OBJECTIVES:
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)
OUTLINE:
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.
Inclusion Criteria:
Histologically proven relapsed or refractory low-grade or follicular CD+ non-Hodgkin lymphoma, including 1 of the following:
Less than 25% bone marrow involvement of cellular marrow with lymphoma by bilateral bone marrow aspirate and biopsy
ECOG performance status 0-2
Bidimensionally measurable disease with at least 1 lesion >= 2 cm in the greatest diameter
No prior myeloablative therapy with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
No concurrent corticosteroid therapy, except prednisone (or equivalent) for adrenal failure or < 20mg of prednisone daily
No prior external beam radiotherapy to >25% of active bone marrow
More than 4 weeks since prior surgery other than diagnostic surgery
No other concurrent myelosuppressive antineoplastic agents
No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan or iodine I 131 monoclonal antibody tositumomab or Lym-1
No CNS lymphoma
No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia
No HIV or AIDS-related lymphoma
No pleural effusion or ascites with lymphoma cells
No active infection
No other serious non-malignant disease that would preclude study participation
No other active primary malignancy
No known human anti-mouse or human anti-chimeric antibody
No prior skin rash (e.g., Stevens-Johnsons syndrome or toxic epidermal necrolysis) from rituximab therapy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Absolute neutrophil count >= 1,500/mm^3
Platelet count >= 150,000/mm^3
Total lymphocyte count < 5,000/mm^3 for patients with small lymphocytic lymphoma
Bilirubin =< 2 mg/dL
Creatinine =< 2 mg/dL