Allogenic Stem Cell Transplantation (SCT) With Non-myeloablative Conditioning in Patients With Relapse Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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To evaluate the use of ibritumomab tiuxetan (Zevalin) as part of the non myeloablative conditioning with melphalan, fludarabine and thiotepa in patients submitted to allogeneic transplantation of haematopoietic stem cells from family donor's peripheral blood.

Official Title
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Allogeneic Transplantation of Haematopoietic Stem Cells Following Non-myeloablative Conditioning With Melphalan, Fludarabine, Thiotepa, Rituximab and Ibritumomab Tiuxetan (Zevalin) in Patients With Aggressive Non-Hodgkin's B-cell Lymphoma

Conditions
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Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Ibritumomab Tiuxetan (Zevalin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Histologically confirmed B-cell lymphoma of the following subtypes: LBCDL Grade 3b follicular lymphoma Mantle-cell lymphoma Transformed B-cell lymphoma Burkitt lymphoma in patients not eligible for a conventional allogeneic transplant High-risk B-cell CD20+ lymphoma defined by Having attained less than PR after two chemotherapy lines Post-transplantation relapse Presence of disease detected through a metabolic approach (PET/CT or else CT+PET) either before or after autologous transplantation Inability to collect enough stem cells for autologous transplantation Stable disease at the time of transplantation Age between 18 and 65 Performance status (ECOG) ≤ 2 Normal and suitable pulmonary function (DLCO ≥ 30%) Left ventricular ejection fraction (LVEF) determined by ventriculography or echocardiogram ≥ 40% Normal hepatic and renal function, with creatinine ≤ 2 mg/dl and Bi ≤ 1.5 mg/dl, and alkaline phosphatase ≤ 2.5 x UNL ; AST, ALT ≤ 2.5 x UNL (≤ 5 x UNL if hepatic infiltration) Exclusion Criteria: Prior treatment with radiopharmaceutical agents HIV-associated lymphoma Presence of human anti-mouse antibodies (HAMA) or anti-chimeric antibodies (HACA) Patient's inability to follow the protocol Hypersensitivity to 90Y-itritumomab tiuxetan Presence of severe pathologies that preclude chemotherapeutic treatment Pregnant women or pregnancy risk due to inappropriate contraceptive measures Breastfeeding 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: 1<br> | Drug: Ibritumomab Tiuxetan (Zevalin)<br>* Conditioning Regimen Rituximab, 250 mg/m2 on days -21 and -14. Ibritumomab tiuxetan (Zevalin): 0.4 mCi/kg (14.8 MBq/kg). Maximum: 32 mCi on day -14. Chemotherapy: Fludarabine 30 mg/m2/day on days -7, -6, -5, -4 and -3 as a 30-min infusion. Melphalan 70 mg/m2/day on days -3 and -2 as a 15-min infusion. Chemotherapy for relapsing patients after autologous transplantation including melphalan over the last 6 months: Thiotepa 5 mg/kg over 4 hours every 12 hours on day -8. Fludarabine 30 mg/m2/day on days -7, -6, -5, -4 and -3 as a 30-min infusion. Melphalan 70 mg/m2/day on day -2 as a 15-min infusion.<br>* Other names: Rituximab (Mabthera);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety (toxicity, transplantation- and graft-related mortality) |  | 36 months | 
| response to treatment according to the Cheson's criteria (Cheson B, et al. JCO 25, 570, 2007). |  | 36 months | 
| overall survival |  | 36 months | 
| relapse rate |  | 36 months | 
| acute and chronic Graft-versus-Host Disease |  | 36 months | 
| haematological and immunological reconstitution, and chimerism. |  | Post transplantation. Once weekly until day +100 and every 2 weeks from day +100. | 
| the impact of Complete Clinical Response, determined by flow cytometry and PET, on progression-free survival |  | 36 months | 

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