Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others, such as yttrium Y 90 ibritumomab tiuxetan, find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving rituximab together with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with yttrium Y 90 ibritumomab tiuxetan works in treating patients with indolent non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine 12-week overall and complete response rate in patients with indolent non-Hodgkin's lymphoma treated with rituximab and yttrium Y 90 ibritumomab tiuxetan as first-line treatment. Secondary Determine 1-year event-free survival of patients treated with this regimen. Determine time to progression and time to next antilymphoma therapy in patients treated with this regimen. Determine the molecular response rate in patients treated with this regimen. Determine the hematological and non-hematological toxicity of this regimen in these patients. Assess the quality of life of patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive rituximab IV followed, no more than 4 hours later, by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day 1. If biodistribution is acceptable, patients receive rituximab IV followed, no more than 4 hours later, by a single dose of yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, or 9 in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, weeks 6, 10, and 14, every 3 months for 2 years, and then every 6 months for 2 years. After completion of study treatment, patients are followed weekly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 18-28 patients will be accrued for this study within 2 years.

Official Title
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A Phase II Study of Yttrium-90-Labeled Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as First Line Treatment in Indolent Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Radiation: yttrium Y 90 ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed indolent non-Hodgkin's lymphoma (NHL), including 1 of the following histologic subtypes: Grade1 or 2 follicular lymphoma Small lymphocytic lymphoma (SLL) Marginal zone B-cell lymphoma CD20-positive disease confirmed by immunohistochemistry or flow cytometry Bidimensionally measurable disease At least 1 lesion measuring ≥ 2.0 cm in a single dimension by CT scan Less than 25% bone marrow involvement with lymphoma by bilateral iliac crest bone marrow aspiration and biopsy within the past 6 weeks No clinically significant impaired bone marrow reserve as evidenced by any of the following: Hypocellular marrow, as evidenced by 1 of the following: ≤ 15% cellularity Marked reduction in bone marrow precursors Platelet count < 100,000/mm^3 Absolute neutrophil count < 1,500/mm^3 History of failed stem cell collection Prior myeloablative therapy No greater than 5,000/mm^3 circulating tumor cells in peripheral blood Requires antilymphoma therapy, as indicated by any of the following: Systemic symptoms B symptoms Cytopenias Malaise Organ compromise Discomfort Pain Disfigurement Rapidly progressive disease Undue anxiety related to not receiving treatment No transformation to intermediate or high-grade NHL No known brain metastases or CNS involvement by lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-2 OR WHO 0-2 OR Karnofsky 70-100% Life expectancy More than 3 months Hematopoietic See Disease Characteristics WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Lymphocyte count < 5,000/mm^3 (for patients with SLL ) Hepatic Bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.5 times upper limit of normal Renal Creatinine ≤ 2.0 mg/dL OR Creatinine clearance > 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Immunologic No anti-murine antibody reactivity (in patients with prior exposure to murine antibodies or proteins) No ongoing or active infection No history of allergic reaction attributed to compounds of similar chemical or biologic composition to yttrium Y 90 ibritumomab tiuxetan Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 1 year after study treatment No other active malignancy except non-melanoma skin cancer No other serious nonmalignant disease that would preclude study participation No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior pegfilgrastim More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior external beam radiotherapy to > 25% of active bone marrow (involved field or regional) Surgery More than 4 weeks since prior major surgery except diagnostic surgery Other No prior systemic antilymphoma therapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer therapy No other concurrent investigational agents No other concurrent antilymphoma therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan<br>Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | Biological: rituximab<br> <br> Radiation: yttrium Y 90 ibritumomab tiuxetan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks | INTERNATIONAL WORKSHOP RESPONSE CRITERIA FOR NON HODGKIN'S LYMPHOMA Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non Hodgkin's lymphoma. J Clin Oncol 1999;17(4):1244-53. | 14 weeks | 
| EFS | Event = Death, second malignancy , disease progression. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, stage I grade 1 follicular lymphoma, stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma