Zevalin-beam for Aggressive Lymphoma

Study Overview
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Brief Summary
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The study hypothesis is that the addition of zevalin radioimmunotherapy to the conditioning regimen given prior to BEAM high-dose chemotherapy and autologous stem cell transplantation in patients with aggressive lymphoma will reduced disease recurrence rate and improve overall and disease-free survival.

Official Title
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SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Relapsed Diffuse Large B-cell Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: ibritumomab tiuxetan
* Procedure: BEAM chemotherapy and autologous stem-cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report. Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease. Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy. Age ≥ 18 years and age ≤ 70 Patients with adequate autologous stem cell collection for transplantation (target ≥ 2.5 x 106 CD34+ cells/kg). Patients must sign written informed consent. Adequate birth control in fertile patients. All prior chemotherapy completed at least three weeks before study treatment. Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed). Negative HIV antibody. Exclusion Criteria: 1. Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy. Two or more relapses after initial response to induction chemotherapy. High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with De Novo Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent all other selection criteria. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit. Creatinine > 2.0 mg/dl. ECOG Performance status > 2. Uncontrolled infection. Pregnancy or lactation. Abnormal lung diffusion capacity (DLCO < 40% predicted). Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2. Active CNS disease involvement. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy > 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer. Pleural effusion or ascites > 1 liter. Known hypersensitivity to rituximab. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate. Prior radioimmunotherapy. Prior autologous or allogeneic HSCT. Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive. Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume. Patients who have received >500cGy radiation to the kidneys will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Z-BEAM<br>ibritumomab tiuxetan (zevalin) BEAM | Drug: ibritumomab tiuxetan<br>* 0.4 mCi/kg<br>* Other names: zevalin;Procedure: BEAM chemotherapy and autologous stem-cell transplantation<br> <br> |
| Active Comparator: standard BEAM<br>standard BEAM chemotherapy | Procedure: BEAM chemotherapy and autologous stem-cell transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | actuarial 2 year survival | 2 years after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | actuarial 2-year PFS | 2 years after transplantation | 
| Clinical Response | complete response (CR) and partial response (PR) proportion at day 100, | 100 days after transplantation | 
| Hematopoietic Recovery | time to hematopoietic recovery | 100 days after transplantation | 
| Grade III Toxicity | incidence of infection, grade III-IV toxicities, treatment-related mortality | 100 days after transplantation | 
| Secondary Malignancies | incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML). | 5 years after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-Hodgkin's lymphoma, autologous stem cell transplantation, radioimmunotherapy, zevalin