Iodine I 131 Tositumomab Followed by Autologous Stem Cell Transplantation in Treating Older Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Combining a radiolabeled monoclonal antibody with autologous stem cell transplantation may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: Phase II trial to study the effectiveness of combining iodine I 131 tositumomab with autologous stem cell transplantation in treating older patients who have relapsed or refractory non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the progression-free survival of older patients with relapsed or refractory non-Hodgkin's lymphoma treated with iodine I 131 tositumomab followed by autologous stem cell transplantation. Secondary Determine the overall survival of patients treated with this regimen. Determine the toxicity and tolerability of this regimen in these patients. OUTLINE: Radioimmunotherapy: Patients receive a test dose of iodine I 131 tositumomab on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over 1 hour on day -14 and are entered into radiation isolation until day -4. Autologous stem cell transplantation: Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients undergoing bone marrow transplantation receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 0 and continuing until blood counts recover. Patients are followed at 1, 3, 6, and 12 months and then annually thereafter. PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within 2 years.

Official Title
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A Phase II Trial Evaluating: Radioiodinated Anti-B1 (Anti-CD20) Antibody With Autologous Stem Cell Transplantation For Relapsed Or Refractory Non-Hodgkin's Lymphoma In Patients 60 Years Of Age And Older

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: sargramostim
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: tositumomab and iodine I 131 tositumomab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma CD20+ disease Failed at least 1 prior standard systemic therapy Persistent lymphoma by physical examination, radiographic studies, bone marrow evaluations, flow cytometry, or polymerase chain reaction Tumor burden less than 500 cc by computed tomography or MRI No splenomegaly Autologous hematopoietic stem cells or bone marrow harvested and cryopreserved No circulating lymphoma cells by morphology or flow cytometry at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSCs are to be used 10% or less marrow involvement by flow cytometry or morphology if purged bone marrow is to be used No CNS lymphoma No chronic lymphocytic leukemia or small lymphocytic lymphoma/well-differentiated lymphocytic lymphoma PATIENT CHARACTERISTICS: Age 60 to 80 Performance status SWOG 0-1 Life expectancy More than 60 days Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 mg/dL Renal Creatinine less than 2.0 mg/dL Cardiovascular No active coronary artery disease Pulmonary FEV_1 at least 70% of expected Vital capacity at least 70% of expected Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative Able to perform self-care during radiation isolation No major organ dysfunction No major infection No circulating anti-mouse antibody No other serious medical condition considered to represent contraindications to bone marrow transplantation No competing causes of death that would predict life span to be less than 10 additional years PRIOR CONCURRENT THERAPY: Biologic therapy No prior bone marrow or stem cell transplantation Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No prior radiotherapy greater than 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or more than 25% of red marrow) Surgery Not specified Other More than 30 days since prior systemic antilymphoma therapy

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: filgrastim|5 µg/kg/day subcutaneously|
|Biological: sargramostim|250µg/m2/d subcutaneously|
|Procedure: autologous bone marrow transplantation|autologous stem cells given via central catheter|
|Procedure: peripheral blood stem cell transplantation|autologous stem cells given via central catheter|
|Radiation: tositumomab and iodine I 131 tositumomab|given intravenously (test dose of 1.7-10 mg/kg tositumomab antibody radiolabeled with  10 mCi I-131) or via central catheter (therapy dose of 1.7-10 mg/kg tositumomab radiolabeled with individually calculated therapy dose of I-131)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival measured continuously |  | from date of transplant through date of death | 

 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 diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma