Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab 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 yttrium Y 90 ibritumomab tiuxetan and rituximab can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. PURPOSE: This phase II trial is studying how well giving yttrium Y 90 ibritumomab tiuxetan together with rituximab works in treating patients with progressive non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the efficacy of yttrium Y 90 ibritumomab tiuxetan and rituximab, in terms of overall response rate (complete, unconfirmed complete, and partial) and duration of response, in patients with transformed CD20+ B-cell non-Hodgkin's lymphoma. Determine the safety of this regimen in these patients. Determine the event-free survival and time to treatment progression in patients treated with this regimen. Determine the immunogenicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive rituximab IV followed within 4 hours by indium In 111 ibritumomab tiuxetan IV (for imaging) over 10 minutes on day 1. Patients undergo 1 (or 2 if needed) imaging scan between days 2-5. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.

Official Title
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A Phase II Study To Evaluate The Safety And Efficacy Of Zevalin (IND # BB IND 4850) Therapeutic Regimen In Patients With Transformed CD20 + B-Cell 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 transformed CD20+ B-cell non-Hodgkin's lymphoma (NHL) Transformation defined as: Progression to a more aggressive diffuse lymphoma, excluding conversion to a more aggressive grade of follicular lymphoma (e.g., WHO/REAL follicular center, large, grade III NHL) Initial large cell follicular lymphoma must progress to a diffuse large cell lymphoma De novo transformed NHL ineligible Requiring treatment as determined by any of the following characteristics: An increase in overall tumor size Presence of B symptoms Presence of masses that are causing ongoing clinical symptomatology Must have less than 25% bone marrow involvement with lymphoma Must have received and either relapsed or failed to respond to prior therapy for initial low grade or follicular NHL Must have bidimensionally measurable disease defined as: Greater than 2 cm OR 1.5 cm if 0.5 cm slices are used during spiral CT scan Nonmeasurable disease includes any of the following: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Lesions that are situated in a previously irradiated area No expected impairment in bone marrrow reserve meeting any of the following criteria: Platelet count less than 150,000/mm^3 Hypocellular bone marrow (less than 15% cellularity) Marked reduction in bone marrow precursors of one or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid) History of failed stem cell collection Patients with peritoneal invasion and/or ascites with positive cytology for lymphoma OR pleural invasion and/or effusion with positive cytology for lymphoma are eligible only if their effusion or ascites can be tapped dry No significant remaining malignant effusion or ascites at the time of study drug administration No known meningeal lymphoma or known parenchymal CNS 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 18 and over Performance status 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Absolute neutrophil count at least 1,500/mm^3 Lymphocyte count no greater than 5,000/mm^3 Platelet count at least 150,000/mm^3 Hepatic Bilirubin no greater than 2.0 mg/dL Renal Creatinine no greater than 2.0 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 year after study treatment HIV negative No other malignancy except nonmelanoma skin cancer unless patient has completed therapy and is considered to be at less than 30% risk of relapse No human anti-mouse antibody (HAMA) reactivity (patients with prior exposure to murine antibodies) PRIOR CONCURRENT THERAPY: Biologic therapy See Radiotherapy At least 3 weeks since prior anticancer immunotherapy (6 weeks for rituximab) and recovered More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF) No prior myeloablative therapy with bone marrow transplantation or peripheral blood stem cell rescue Chemotherapy See Biologic therapy At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered Endocrine therapy No concurrent systemic corticosteroids with either of the following dose schedules: No greater than 50 mg of prednisone as a single dose (or equivalent) No greater than 50 mg of prednisone per dose (or equivalent) for more than 6 doses Radiotherapy See Disease Characteristics At least 3 weeks since prior anticancer radiotherapy and recovered No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan No prior external beam radiotherapy to more than 25% of active bone marrow (involved field or regional) Surgery At least 3 weeks since prior anticancer surgery and recovered More than 4 weeks since prior major surgery (other than diagnostic surgery) Other At least 3 weeks since other prior anticancer therapy and recovered

Ages Eligible for Study
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Minimum Age: 18 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 + yttrium Y 90 ibritumomab tiuxetan<br>Patients receive rituximab IV followed within 4 hours by yttrium Y 90 ibritumomab tiuxetan IV (for imaging) over 10 minutes on day 1. Patients undergo 1 (or 2 if needed) imaging scan between days 2-5. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years. | 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 |
| --- | --- | --- |
| Overall response rate |  | Up to 4 years | 
| Duration of response |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR), unconfirmed CR, and partial response |  | Up to 4 years | 
| Event-free survival |  | Up to 4 years | 
| Time to progression |  | Up to 4 years | 
| Time to next lymphoma treatment |  | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma