Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

Study Overview
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Brief Summary
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Phase I/II trial to study the effectiveness of combining yttrium Y 90 ibritumomab tiuxetan with rituximab in treating patients who have localized or recurrent lymphoproliferative disorder after an organ transplant. 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

Detailed Description
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OBJECTIVES: I. Determine the safety and tolerability of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) in patients with post-transplant lymphoproliferative disorder. II. Determine the safety and toxicity profile of IDEC-Y2B8 and rituximab in these patients. III. Correlate the Epstein-Barr virus viral load with response and relapse in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8). Phase I: Patients receive rituximab IV and indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-6. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by IDEC-Y2B8 IV over 10 minutes on day 8.Cohorts of 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 no more than 1 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive treatment as in phase I at the MTD of IDEC-Y2B8. 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 I/II Study: Zevalin Radioimmunotherapy for Patients With Post Transplant Lymphoproliferative Disease Following Solid Organ Transplantation

Conditions
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Post-transplant Lymphoproliferative Disorder, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Waldenström Macroglobulinemia

Intervention / Treatment
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* Biological: rituximab
* Radiation: indium In 111 ibritumomab tiuxetan
* Radiation: yttrium Y 90 ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed post-transplant lymphoproliferative disorder (PTLD) of 1 of the following stages: Stage III or IV Localized (not amenable to localized radiotherapy or excision) Recurrent The following histologies* are eligible: Polyclonal PTLD Monoclonal PTLD Diffuse large B-cell non-Hodgkin's lymphoma (NHL) Lymphoplasmacytic NHL Burkitt/Burkitt-like NHL Must not have completely responded during OR progressed after prior rituximab with or without chemotherapy No history of rapid disease progression while receiving prior chemotherapy Measurable disease Must have less than 25% bone marrow involvement with lymphoma Prior solid organ transplantation required Evaluation of malignant cells for Epstein-Barr virus (EBV) required EBV positive or negative allowed No pleural effusion No CNS lymphoma, including leptomeningeal disease No pulmonary involvement by NHL in patients with prior lung transplantation No HIV or AIDS-related lymphoma No hypocellular bone marrow (i.e., less than 15% cellularity) No marked reduction in bone marrow precursors of one or more cell lines (i.e., granulocytic, megakaryocytic, or erythroid) Performance status - Karnofsky 50-100% At least 3 months Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Bilirubin no greater than 2.5 mg/dL Creatinine no greater than 2.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation HIV negative No serious nonmalignant disease or infection that would compromise study objectives No presence of antimurine antibody reactivity No other concurrent active malignancy requiring therapy More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF) More than 6 weeks since prior rituximab No prior allogeneic bone marrow or hematopoietic stem cell transplantation No prior radioimmunotherapy for NHL More than 4 weeks since prior chemotherapy See Biologic therapy No prior radiotherapy to more than 25% of active bone marrow (involved field or regional) More than 4 weeks since prior major surgery except diagnostic surgery No other concurrent anticancer therapy

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: Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)<br>Phase I: Patients receive rituximab IV and indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-6. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by IDEC-Y2B8 IV over 10 minutes on day 8. Phase II: Patients receive treatment as in phase I at the MTD of IDEC-Y2B8. Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years. | Biological: rituximab<br>* Given IV<br>* Other names: Rituxan;Radiation: indium In 111 ibritumomab tiuxetan<br>* Given IV<br>* Other names: IDEC-In2B8;Radiation: yttrium Y 90 ibritumomab tiuxetan<br>* Given IV<br>* Other names: Y90-labeled ibritumomab tiuxetan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Estimated using binomial proportions and their 95% confidence intervals. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | Analyzed by the Kaplan-Meier non-parametric methods. | Up to 4 years | 
| Time to progression | Analyzed by the Kaplan-Meier non-parametric methods. | From the date of first study treatment to the first date when progressive disease is documented, assessed up to 4 years | 
| Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0 | Presented by severity for each dose group. | Up to 4 years |