Monoclonal Antibody Therapy in Relapsed Non-Hodgkin's After Chemotherapy and Autologous Stem Cell Transplantation

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Radiolabeled monoclonal antibodies can locate and deliver radioactive cancer-killing substances. PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibodies with rituximab in treating patients who have non-Hodgkin's lymphoma that has not responded to high-dose chemotherapy and autologous stem cell transplantation.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of yttrium Y 90-labeled ibritumomab tiuxetan when administered with rituximab in patients with B-cell non-Hodgkin's lymphoma who have relapsed after high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Determine the safety and efficacy of this regimen in these patients. OUTLINE: This is a dose-escalation study of yttrium Y 90-labeled ibritumomab tiuxetan (IDEC-Y2B8). Phase I: Patients receive rituximab IV over 4-6 hours followed by indium In 111-labeled ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients receive rituximab IV again on day 7 followed by IDEC-Y2B8 IV over 10 minutes. Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity. Phase II: Once the MTD is determined, 58 additional patients are treated at that dose level as in phase I. Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 78 patients (20 for phase I and 58 for phase II) will be accrued for this study within 2 years.

Official Title
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Phase I/II Study of IDEC-Y2B8 (Zevalin) for Post Transplant Relapses of 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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Inclusion Criteria: Diagnosis of relapsed B-cell non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous stem cell transplantation Less than 25% bone marrow involvement with NHL as evidenced by unilateral or bilateral biopsy within the past 6 weeks o Bone marrow biopsy should demonstrate 15-20% of cellular space occupied by normal hematopoiesis CD20 antigen expression in tumor tissue within the past year as evidenced by 1 of the following: Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody Flow cytometry studies Measurable disease o More than 2 cm bidimensionally 19 years of age and over Performance status WHO 0-2 Life expectancy at least 3 months Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 150,000/mm^3 Bilirubin less than 2.0 mg/dL SGOT or SGPT no greater than 2.5 times upper limit of normal (unless due to lymphomatous infiltration of the liver) Creatinine less than 2.0 mg/dL Fertile patients must use effective contraception during and for 6 months after study therapy HIV negative At least 4 weeks since prior growth factors At least 4 weeks since prior biologic therapy At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas) At least 4 weeks since prior radiotherapy Recovered from all prior therapy At least 4 weeks since prior immunosuppressants Exclusion Criteria: No active CNS lymphoma No HIV- or AIDS-related lymphoma No transfusion dependency No active obstructive hydronephrosis Not pregnant or nursing/negative pregnancy test No active infection requiring oral or IV antibiotics No human antimurine antibody positivity No other major medical problems No dependency on hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim [G-CSF], or sargramostim [GM-CSF]) No prior radioimmunotherapy No other concurrent biologic therapy of any kind No prior fludarabine No concurrent chemotherapy No concurrent steroids except as maintenance for non-cancerous disease No prior pelvic radiotherapy No prior radiotherapy to more than 25% of estimated bone marrow reserve No concurrent external beam radiotherapy No other concurrent investigational drugs No other concurrent anti-cancer therapy

Ages Eligible for Study
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Minimum Age: 19 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

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Radiation: yttrium Y 90 ibritumomab tiuxetan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 
| Safety and efficacy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma