Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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Despite of the availability of treatment for this disease, this study is justified because no known therapies are really curative and it is necessary to look for new treatment options to improve the clinical outcome and prognosis of relapsed aggressive lymphoma. This study is designed for patients not eligible for high-dose chemotherapy and autologous stem cells transplantation.

Detailed Description
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The objectives of this study are to evaluate the efficacy and safety of two sequential doses of 90Y-Ibritumomab Tiuxetan administered after salvage chemotherapy in patients with relapsed/refractory aggressive lymphoma non-eligible for HDC and ASCT.

Official Title
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Two Repeated Doses of Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) as Salvage Treatment for Patients With Relapsed or Refractory Aggressive B-cell Lymphoma: a Phase II Study.

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: 90Y-Ibritumomab Tiuxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 Diagnosis of CD20+ B-diffuse large cell de novo or transformed or follicular lymphoma grade IIIb Stage II, III, IV according to Ann Arbor criteria Chemoresistant disease after first line treatment (CHOP-like + Rituximab) or relapsed patients after one or two lines of chemotherapy not-eligible for high dose chemotherapy and autologous stem cell transplantation Performance status 0-2 according to WHO criteria HIV negativity Normal liver, lung and kidney function: conjugated bilirubin up to 2 x ULN, alkaline phosphatase and transaminases up to 2 x ULN, creatinine clearances ≥45 ml/min Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 150 x 109/l and bone marrow involvement < 25% before first Zevalin infusion. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 100 x 109/l before second Zevalin infusion Use of effective contraception for the entire treatment period in patients sexually active Negative pregnancy test in child bearing potential women Life expectancy > 6 months Written informed consent Exclusion Criteria: More than two lines of prior chemotherapy before study entry Prior high dose chemotherapy and autologous stem cell transplantation HIV positivity HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis Pregnant or breastfeeding CNS lymphoma involvement. History of malignant carcinoma within the last 3 years other than squamous cell and basal cell carcinoma. Cardiac failure with VEF < 40% Clinical evidence of not controlled infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: 90Y-Ibritumomab Tiuxetan double dose<br>90Y-Ibritumomab Tiuxetan administered at 0.4 mCi/kg at phase 2 and then at 0.2 mCi/kg at phase 3 | Drug: 90Y-Ibritumomab Tiuxetan<br>* All patients receive 2 courses of age-adjusted R-miniDHAP followed by two doses of 90Y-Ibritumomab Tiuxetan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| An interim analysis on all the available data after the enrolment of the 15th patient (completion of the 1st stage) will be conducted, both for safety and efficacy. |  | after the enrolment of the 15th patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| after the interim analysis, the writing committee of the study will evaluate to increase the second dose of Zevalin to 0.3 mCi/Kg. The same procedure will be applied to decide if the trial must be stopped after the enrolment of the 23rd patient. |  | after the enrolment of the 23rd patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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two sequential doses of 90Y-Ibritumomab Tiuxetan