Y 90 Ibritumomab Tiuxetan &Rituximab Relapsed or Refractory Diffuse Large B-Cell 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. Combining yttrium Y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining yttrium Y 90 Ibritumomab tiuxetan with rituximab in treating patients who have relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the best overall response in patients with relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma treated with yttrium Y 90 ibritumomab tiuxetan and rituximab. Determine the event-free survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Radioimmunotherapy: Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for imaging only); yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8; and rituximab IV over 3-4 hours on days 1, 8, 15, 22, 29, and 36. CNS ( central nervous system)prophylaxis: Patients receive CNS prophylaxis comprising intrathecal (IT) methotrexate or IT cytarabine on days 15, 22, 29, and 36 OR IT cytarabine (liposomal) on days 15 and 29. Maintenance rituximab: Patients are assessed for response at week 14. Beginning at month 6, patients with stable or responding disease receive maintenance therapy comprising rituximab IV over 3-4 hours once weekly for 4 weeks. Maintenance therapy repeats every 6 months for 2 years (total of 4 courses) in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

Official Title
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Zevalin And Rituxan For The Treatment Of Relapsed Or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma, including any of the following: B-cell diffuse large cell variant Immunoblastic Mediastinal (thymic) large cell T-cell/histiocyte-rich Anaplastic large B-cell Intravascular large B-cell Lymphomatoid granulomatosis Relapsed or refractory disease after at least 1 prior chemotherapy regimen and requires further treatment Relapsed disease, defined as the following: Appearance of any new lesion OR increase of at least 50% in the size of a previously involved site 50% increase in greatest diameter of any previously identified node greater than 1 cm in the short axis OR in the sum of the perpendicular diameter (SPD) of more than 1 node Progressive disease, defined as the following: 50% increase from nadir in the SPD of any previously identified abnormal node Appearance of any new lesion during or at the end of therapy CD20-positive disease by immunohistochemistry Bidimensionally measurable disease At least 1 lesion at least 2.0 cm by CT scan Less than 25% bone marrow involvement by lymphoma No transformed lymphoma from indolent to aggressive No HIV- or AIDS-related lymphoma No hypocellular bone marrow No marked reduction in bone marrow precursors of 1 or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid) No CNS lymphoma Ineligible for myeloablative therapy OR refused transplantation Ineligible for any other open yttrium Y 90 ibritumomab tiuxetan investigational protocols PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Lymphocyte count no greater than 5,000/mm^3 (for patients with small lymphocytic lymphoma) Platelet count at least 100,000/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 participation No concurrent serious nonmalignant disease or infection that would preclude study participation No human antimurine antibody reactivity PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior autologous bone marrow transplantation No prior peripheral blood stem cell rescue No prior failed stem cell collection Prior rituximab within the past 90 days allowed provided patient has fludeoxyglucose-avid disease that is also indium In 111 ibritumomab tiuxetan-avid disease in at least 1 lesion More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy No prior radioimmunotherapy No prior external beam radiotherapy (involved field or regional) to more than 25% of active bone marrow Surgery More than 4 weeks since prior major surgery (except diagnostic surgery) Other Recovered from all prior therapy More than 4 weeks since prior therapy for lymphoma More than 8 weeks since prior phase II investigational drugs No other concurrent antineoplastic 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
Interventional Model Description: Standard Phase 2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-90 Ibritumomab Tiuxetan<br>Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab and central nervous system prophylaxis with Cytarabine or liposomal cytarabine | Biological: rituximab<br> <br> * Other names: Rituxan;Drug: cytarabine<br>* to be used for CNS prophylaxis<br>* Other names: cytosine arabinoside;Drug: liposomal cytarabine<br>* to be used as CNS prophylaxis<br>* Other names: Depocyte;Radiation: yttrium Y 90 ibritumomab tiuxetan<br> <br> * Other names: Zevalin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate = Complete and Partial Response at 12 Weeks. | Definition Nodal Masses Spleen, Liver Bone Marrow CR Disappearance of all evidence of disease Partial response Regression and no new sites ≥ 50% decrease in sum of the perpendicular dimension of up to 6 largest dominant masses; no increase in size of other nodes Stable disease Failure to attain CR/PR or Progressive disease or Relapsed disease : the appearance of any new lesion or the (a) FDG-avid or PET positive prior to therapy; PET positive at prior sites of disease and no new sites on CT or PET Any new lesion or increase by ≥ 50% of previously involved sites from nadir Appearance of a new lesion(s) > 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥ 50% increase in longest diameter of a previously identified node > 1 cm in short axis > 50% increase from nadir in the SPD of any previous lesions New or recurrent involvement Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy | 12 weeks | 
| Best Response | This data is the best overall response achieved by patients by the 12 month period. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival | the median time point at which a participants experienced and event or toxicity or progression | 12 months | 

 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 immunoblastic large cell lymphoma, anaplastic large cell lymphoma