Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Primary Central Nervous System Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This phase II trial studies how well yttrium Y 90 ibritumomab tiuxetan and rituximab work in treating patients with recurrent or refractory primary central nervous system non-Hodgkin lymphoma. Radiolabeled monoclonal antibodies, such as yttrium 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving yttrium Y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the radiographic response proportion in patients with refractory or recurrent primary central nervous system lymphoma (PCNSL) to ibritumomab tiuxetan (yttrium Y 90 ibritumomab tiuxetan) when given as an intravenous infusion. SECONDARY OBJECTIVES: I. Determine the progression free survival of patients treated with ibritumomab tiuxetan when given as an intravenous infusion. II. Determine the overall survival of patients treated with ibritumomab tiuxetan when given as an intravenous infusion. III. Establish the toxicity profile of ibritumomab tiuxetan in this patient population. IV. Use positron emission tomography (PET)/magnetic resonance imaging (MRI) to map the distribution of Y-90 ibritumomab tiuxetan, and calculate the Gy delivered based on the activity found within tumor. OUTLINE: Patients receive rituximab intravenously (IV) on day 1. Within 7 to 9 days, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV in the absence of disease progression or unacceptable toxicity. Distribution and dose absorbed dose will be assessed on day 11. Quality of life will be assessed at screening, at day 1, 36, 92, and at each follow-up visit. After completion of study treatment, patients are followed every 3-6 months for 2 years.

Official Title
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Phase II Study of Radioimmunotherapy With Zevalin (Ibritumomab Tiuxetan) Therapy for Patients With Refractory or Relapsed Primary Central Nervous System Lymphoma (PCNSL)

Conditions
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Primary Central Nervous System Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Radiation: yttrium Y 90 ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histological diagnosis of recurrent or refractory primary central nervous system (CNS) lymphoma with at least 1 measurable gadolinium enhancing lesion on brain MRI scans Karnofsky performance status (KPS) >= 60 Patients could not have had more than 3 prior therapy regimens for the treatment of PCNSL Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Platelets >= 100 x 10^9/L Hemoglobin (Hgb) > 10 g/dL Serum total bilirubin =< 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) =< 3.0 x ULN Aspartate aminotransferase (AST) =< 3.0 x ULN Serum creatinine =< 1.5 x ULN Minimum interval since completion of radiation treatment is 12 weeks Minimum interval since last drug therapy: 3 weeks since the completion of non-cytotoxic agents 4 weeks since the completion of a non-nitrosourea-containing regimen 6 weeks since the completion of a nitrosourea-containing regimen Patients must have signed an approved informed consent and authorization permitting release of personal health information Patients are not on corticosteroids or on stable doses (less than 6 mg daily of dexamethasone) for more than 1 week before baseline imaging Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission; patients with other prior malignancies must be disease-free for >= three years Exclusion Criteria: Pregnant or breast-feeding women Patients unwilling or unable to comply with the protocol Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness, etc.) that could cause unacceptable safety risks or compromise compliance with the protocol Known diagnosis of human immunodeficiency virus (HIV) infection; prior radioimmunotherapy, prior myeloablative therapy with autologous bone marrow transplantation or peripheral stem cell rescue, and prior external beam radiation therapy to more than 25% of active bone marrow Patients who have received filgrastim (G-CSF) or sargramostim (GM-CSF) within 2 weeks before treatment or major surgery within the prior 4 weeks

Ages Eligible for Study
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Minimum Age: 18 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: rituximab and yttrium Y 90 ibritumomab tiuxetan<br>Patients receive rituximab IV on day 1. Within 7 to 9 days, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV in the absence of disease progression or unacceptable toxicity. | Biological: rituximab<br>* Given IV<br>* Other names: Rituxan;Radiation: yttrium Y 90 ibritumomab tiuxetan<br>* Given IV<br>* Other names: Y90-labeled ibritumomab tiuxetan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Response Assessed by MRI or FDG-PET/MRI | Number of patients with at least a 50% reduction in tumor size on a MRI scan with stable or decreasing dose of corticosteroids | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The number of patients without an unequivocal increase in tumor size or the appearance of new lesions by MRI | Up to 2 years | 
| Overall Survival | The number of patients alive up to two years after treatment | Up to 2 years | 
| Establish the Toxicity Profile of Ibritumomab Tiuxetan in This Patient Population. | Number of patients with toxicities related to the study drug | Up to 30 days following the last dose of study treatment | 
| Dosimetry Calculations of Yttrium Y 90 Ibritumomab Tiuxetan Assessed by PET/MRI | Number of Gy delivered to each tumor as calculated using the MIRD dosimetry formula on PET data | At day 11 |