Zevalin Plus BuCyE High-dose Therapy in B-cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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In order to improve the clinical result of high-dose chemotherapy and autologous stem cell transplantation for B-cell non-Hodgkin's lymphoma, Zevalin will be added to the conditioning regimen. Investigators expect this radioimmunotherapy of Zevalin plus busulfan, cyclophosphamide and etoposide regimen will improve survival of relapsed or poor-risk B-cell non-Hodgkin's lymphoma.

Detailed Description
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Title: Combining 90Y-Ibritumomab tiuxetan (Zevalin) with high-dose chemotherapy of BuCyE and autologous stem cell transplantation in patients with relapsed, refractory, or high-risk B-cell non-Hodgkin's lymphoma - an open-labeled phase II study. Study design: Prospective, multicenter, open-labeled, phase II trial. Study objectives: Primary: event-free survival time following autologous stem cell transplantation with 90Y-Ibritumomab tiuxetan and BuCyE high-dose chemotherapy in patients with relapsed, refractory, or high-risk B-cell non-Hodgkin's lymphoma Secondary: overall survival response rate toxicity of the treatment combination Treatment: Z-BuCyE Regimen Day 21: rituximab, 250 mg/m2, I.V. Day 14: rituximab, 250 mg/m2, I.V. 90Y-Ibritumomab tiuxetan, 0.4 mCi/kg, I.V. Day 7, 6, 5: busulfan 3.2 mg/kg I.V. Day 5, 4: etoposide 200 mg/m2 I.V. every 12 hours Day 3, 2: Cytoxan 50 mg/kg I.V. Day 0: autologous stem cell infusion

Official Title
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Combining 90Y-ibritumomab Tiuxetan With High-dose Chemotherapy of BuCyE and Autologous Stem Cell Transplantation in Patients With B-cell Non-Hodgkin's Lymphoma - an Open-labeled Phase II Study

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Zevalin-BuCyE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed B-cell NHL in chemotherapy-sensitive relapse, in partial response to 1st line chemotherapy, or in complete response after 1st line chemotherapy with high IPI score at diagnosis Age < 65 years old WHO performance status (PS) of 0-2 ANC > 1,500/mm3, platelet > 100,000/mm3 Cr < 2.0 mg% or Ccr > 50 mL/min Transaminase < 3X upper normal value Bilirubin < 2 mg/dL Life expectancy of at least 3 months Written informed consent Optimal harvest of autologous stem cells (CD34+ cells > 5 million/kg plus 2 million/kg for back-up) Exclusion Criteria: Prior hematopoietic stem cell transplantation Prior RIT Prior external radiation to > 25% of active bone marrow CNS involvement of non-Hodgkin's lymphoma Serious comorbid diseases HIV or HTLV-1 associated malignancy History of other malignant disease in the previous 5 years, except squamous cell or basal cell carcinoma of skin or stage I uterine cervical carcinoma or cervical carcinoma in situ Known hypersensitivity to murine antibodies/proteins Pregnant or breast feeding female patients, adults without effective contraception up to 12 months after RIT Persistent toxic side effects from prior therapy Prior biologic or immunotherapy less than 4 weeks prior to entry on this study Investigational drugs less than 4 weeks prior to entry on this study

Ages Eligible for Study
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Maximum Age: 64 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: Zevalin-BuCyE<br>histologically confirmed, relapsed or refractory CD20 positive B-cell NHL including diffuse large B-cell, follicular, mantle cell, and Burkitt lymphomas. | Drug: Zevalin-BuCyE<br>* rituximab (IV, 250 mg/m2 on days -21 and -14) single dose of 90Y-ibritumomab (IV, 0.4 mCi/kg on day -14) Busulfan (IV, 0.8 mg/kg every 6 h from day -7 to day -5) Cyclophosphamide (IV, 50 mg/kg on days -3 and -2) Etoposide (IV, 200 mg/m2 every 12 h on days -5 and -4) Autologous stem cells infusion on day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Three year event-free survival rate would be reported. | the time from stem cell infusion to failure or death from any cause | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Three year overall survival would be reported. | from stem cell infusion to death of any cause or last follow-up | 
| Toxicity of the treatment combination | Adverse events would be assessed and graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), version 3.0. And the frequency of each grade would be reported as case number and proportion. | any toxicity due to study treatment during study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zevalin, B-cell non-Hodgkin's lymphoma, autologous stem cell transplantation, BuCyE regimen