A Study of Zevalin and Simultaneous Application of BEAM High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Refractory and Relapsed Aggressive Non-Hodgkin Lymphomas

Study Overview
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Brief Summary
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Phase II Study Concomitant High-Dose Radio-Immuno- and Chemotherapy with simultaneous application of Zevalin and BEAM followed by autologous peripheral stem cell transplantation in relapsed and refractory CD 20+ Non-Hodgkin's lymphoma

Official Title
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Phase I/II Study Concomitant High-Dose Radio-Immuno- and Chemotherapy With Simultaneous Application of Zevalin and BEAM Followed by Autologous Peripheral Stem Cell Transplantation in Relapsed and Refractory CD 20+ Non-Hodgkin's Lymphoma

Conditions
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Primary Non-Hodgkin-Lymphoma, Refractory Non-Hodgkin-Lymphoma, CD20+ Aggressive Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Zevalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 - 65 years Risk group: 1) Progression on primary therapy 2) Initial or subsequent relapse Histology: Diagnosis of relapsed aggressive non-Hodgkin lymphoma, whenever possible confirmed by an excision biopsy of a lymph node or by a sufficiently large biopsy of an extranodal site if no lymph node lesion is present. The expression of the CD20 antigen must be demonstrated in the primary lesion or in the relapse. Specifically, the following entities can be treated in this study: B-NHL: Grade III B follicular lymphoma Diffuse B-cell lymphoma centroblastic immunoblastic plasmoblastic anaplastic-large-cell T-cell rich B-cell lymphoma Primary effusion lymphoma Intravascular B-cell lymphoma Primary mediastinal B-cell lymphoma Mantle cell lymphoma, blastoid Variants of Burkitt's lymphoma Aggressive marginal zone lymphoma (monocytoid) General condition: General condition ECOG 0-3 (Karnofsky: 40 - 100 %); for definition see Annex 14.10 Presence of declaration of participation of the center and the patient's written consent form Exclusion Criteria: Prior mediastinal or extensive abdominal irradiation Prior high-dose therapy and autologous stem cell transplantation Impairment of renal function (creatinine > 2.5 mg/dL, creatinine clearance < 20 mL/min) Impairment of hepatic function (bilirubin > 2.0 mg/dL, cholinesterase [CHE] < 2000 U/L) Impairment of pulmonary function (transfer lung factor for CO [TLCO] < 50 %, forced expiratory volume in 1 sec [FEV1] < 60 %, vital capacity [VC] < 60 %) Relevant deterioration of the above organ functions on salvage therapy Failure of stem cell mobilization Active viral hepatitis HIV infection Other active or not conclusively curatively treated malignoma Severe concomitant psychiatric illness or suspected lack of patient compliance Pregnancy or unreliable contraception Highly dynamic progress of lymphoma (lactate dehydrogenase [LDH] > 1.5 x upper limit of normal [ULN]) after salvage therapy immediately prior to radioimmunotherapy

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Zevalin<br>* All applications of 90Y-Ibritumomab-Tiuxetan will be preceded by rituximab infusions at a dose of 250 mg/m2 at days -21 and day -14 (DL1) or day -12 (DL2) or day -10 (DL3-5), respectively. High dose therapy will be given as BEAM<br>* Other names: 90Y-Ibritumomab-Tiuxetan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome variable is the highest achievable dose level of 90Y-Zevalin administered immediately before BEAM high-dose therapy and followed by autologous stem cell transplantation. |  | 3 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related mortality (TRM), freedom from progression (FFP), Survival (OS), progression free survival (PFS) grade III -IV toxicity (CTC) on lung, liver and kidney |  | 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-Dose Radio-Immuno- and Chemotherapy, stem cell transplantation, 90Y-Ibritumomab-Tiuxetan