Targeted Intensification With ZBEAM and Autologous Stem Cell Transplantation in Patients With High-grade B-Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and the safety of a preparative regimen utilizing standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy combined with high-dose BEAM followed by ASCT after first line treatment in patients aged from 18 to 65 years with poor prognosis CD 20 Diffuse Large B-Cell lymphoma

Official Title
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Targeted Intensification by a Preparative Regimen for Patients With High-grade B-Cell Lymphoma Utilizing Standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-dose BEAM Followed by Autologous Stem Cell Transplantation (ASCT)

Conditions
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Lymphoma, Large Cell, Diffuse

Intervention / Treatment
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* Drug: ZBEAM (Zevalin, BCNU, Etoposide, Aracytine, Melphalan)
* Procedure: ASCT
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged from 18 to 65 years. Patient with pathologically proven, high grade B-cell Lymphoma CD 20 positive (WHO classification) : Diffuse large B cell lymphoma. Adverse prognostic factors IPI>1 In Complete Remission, or partial response to first line treatment. Previously treated with chemotherapy regimen containing rituximab: R CHOP or R ACVBP Chemo-sensitive disease PET Scan prior transplant Eligible for autologous stem cell transplantation With a minimum life expectancy of 3 months. Negative HIV, HBV and HCV serologies (in the last 4 weeks except after vaccination). Having previously signed a written informed consent. Exclusion Criteria: Histological transformation in diffuse large B cell lymphoma, any type of low grade lymphoma More than one line of treatment. Prior transplantation. Prior exposure to Zevalin Central nervous system or meningeal involvement by lymphoma. Contraindication to any drug contained in the chemotherapy regimen. Any serious active disease or co-morbid medical condition (according to the investigator's decision and information provided in the IDB). Poor renal function (creatinin level up to 2.5 maximum normal level) unless these abnormalities are related to the lymphoma. Poor hepatic function (total bilirubin level up to 30 micro mol/l, transaminases up to 2.5 maximum normal level) unless these abnormalities are related to the lymphoma. Poor bone marrow reserve as defined by neutrophils less than 1.5 G/l or platelets less than 100 G/l Large bone marrow irradiation more than 40percent. Bone marrow infiltration Lack of sufficient autologous hematopoietic stem cells for transplantation. Prior treatment with murine antibodies Known hypersensibility to murine antibodies or proteins Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study. Adult patient unable to give informed consent because of intellectual impairment. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Experimental<br>ZBEAM (Zevalin, BCNU, Etoposide, Aracytine, Melphalan) ASCT Rituximab | Drug: ZBEAM (Zevalin, BCNU, Etoposide, Aracytine, Melphalan)<br>* Zevalin 0.4 mCi/kg: D-14 BCNU 300 mg/m² : D-6 Etoposide 100 mg/m²/12h : D-6 D-5 D-4 D-3 Aracytine 200 mg/m²/12h : D-6 D-5 D-4 D-3 Melphalan 140 mg/m²: D-2<br>Procedure: ASCT<br>* ASCT : D0<br>Drug: Rituximab<br>* Rituximab 250 mg/m² :D-21 D-14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival (EFS): events being death from any cause, relapse for complete responders and unconfirmed complete responders, progression during and after treatment and changes of therapy |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) (Complete Response CR and Partial Response PR) | 100 days after ASCT | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Lymphoma Diffuse, B-Cell lymphoma, Aggressive lymphoma