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

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.

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