Transplantation With Ybritumomab Tiuxetan (Zevalin) Plus BEAM Regimen in Patients With Refractory Large B-cell Difusse Lymphom

Study Overview
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Brief Summary
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To evaluate the efficacy (complete response rate) of Ybritumomab Tiuxetan (Zevalin) administration in the conditioning treatment of patients with refractory large B-cell diffuse lymphoma submitted to autologous transplantation of peripheral blood haematopoietic stem cells.

Official Title
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Autologous Transplantation of Haematopoietic Stem Cells With Conditioning Including Zevalin + BEAM to Patients Suffering From Refractory Large B-cell Diffuse Lymphom

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Ybritumomab Tiuxetan (Zevalin); Rituximab; BEAM (BCNU, ARAC, VP16 and Melphalan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Give their written informed consent. Abide by at least one of the following conditions: Obtain no partial response after first-line chemotherapy including anthracyclines + rituximab (R-CHOP, R-MegaCHOP, R-EPOCH or the like), or else Absence of partial response after having received salvage (post-induction) chemotherapy including R-IFE, R-ESHAP, R-ICE or the like. Patients on first recidivation who do not attain partial remission after salvage chemotherapy. Patients with transformed lymphoma, on first partial remission (No CR). Stable disease at the time of transplantation. Age ≥ 18 but ≤ 70. Life expectancy of greater than three months. Additionally, to be able to undergo haematopoietic stem cell transplantation, all patients should satisfy the requirements of routine clinical practice, i.e.: Performance status (ECOG) < 3. FEV1, DLCO and FVC ≥ 50% of the normal theoretical values. Ventricular ejection fraction (through echocardiography or isotope ventriculography) ≥ 50%. Total bilirubin and transaminases < 3 times the normal maximum value, except if attributable to the underlying disease. Creatinine < 2 times the maximum normal value, and creatinine clearance > 40 ml/min, except if attributable to the underlying disease. Absence of symptomatic heart disease, cirrhosis or active B or C virus hepatitis. HIV negative. Exclusion Criteria: Impossibility of collecting, via apheresis, a number of CD34+ cells ≥ 2 x 106/kg. Known hypersensitivity to mouse proteins. Involvement of CNS by lymphoma. Progressive lymphoma during the month prior to the date of transplantation. Previous radioimmunotherapy. Previous autologous transplantation of haematopoietic stem cells. Pregnant or breastfeeding women, or adults of childbearing age who are not using an effective contraceptive method. Being submitted to treatment in a clinical trial for 30 days prior to entry in this trial. Active psychiatric disease, including addiction disorders. Existence of active not-haematopoietic neoplasia, with the exception of cutaneous basal carcinoma or cervix intraepithelial carcinoma.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>BEAM preceded by Ybritumomab Tiuxetan (Zevalin) | Drug: Ybritumomab Tiuxetan (Zevalin); Rituximab; BEAM (BCNU, ARAC, VP16 and Melphalan)<br>* Day -21: rituximab. 250 mg/m2 iv Day -14: rituximab. 250 mg/m2 plus Ybritumomab Tiuxetan (Zevalin)(0.4 mCi/kg maximum dose 32 mCi). Days -6 to -1: BEAM regimen as follows BCNU: 300 mg/m2 over 2 hours, day -6. ARAC: 200 mg/m2/12 hours over 12 hours, days -5 through -2. VP16: 200 mg/m2/day over 2 hours, days -5 through -2. Melphalan: 140 mg/m2/day over 15 minutes, day -1.<br>* Other names: Rituximab (Mabthera);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease clinical response to treatment - complete response rate. |  | Pre-transplantation; post-transplantation (one week following Ybritumomab Tiuxetan (Zevalin) administration); And three months post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematopoietic and extra-haematopoietic toxicity of the Ybritumomab Tiuxetan (Zevalin) plus BEAM regimen. |  | 36 months | 
| Overall response rate (complete + partial response) |  | 36 month | 
| Progression-free-survival |  | 36 month | 
| Overall survival |  | 96 months | 
| Post-transplantation haematological and immunological reconstitution |  | Until post-transplantation day +100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Z-BEAM, Autologous, Lymphoma, GELTAMO