Treatment of Recurrent Primary or Secondary Central Nervous System (CNS) Lymphoma With ALIMTA (Pemetrexed)

- Since we are looking for the highest dose of pemetrexed that can be given to people
safely, not everyone who participates in this study will be receiving the same amount
of the study drug. The dose participants will receive will depend upon the number of
people that have been enrolled on the study before them and how well they have
tolerated their doses of the study drug.

- Pemetrexed is given into a vein (by IV) over a 10 to 20 minute period once every 14
days. This 14 day period is called a cycle of study treatment.

- Study treatment will be divided into three phases. Induction: Participants will be
given a maximum of 8 cycles. If the participant does not achieve a complete response
after eight induction cycles, they will be taken off study. A complete response means
there is no evidence of disease on MRI or CT scan. Consolidation: If the participant
has achieved complete response, they will have two additional cycles. Maintenance:
Following the completion of the consolidation cycles, participants will receive the
study drug only once per month. They can continue to receive maintenance cycles for up
to a year from the start of the first induction cycle.

- Folic acid and vitamin B12 are two vitamins that have been shown to help lessen the
severity of some side effects of pemetrexed. Participants will begin taking oral folic
acid tablets at least 5 days before their first dose of pemetrexed and daily until 3
weeks after their last dose. Vitamin B12 is given through injections into your muscle.
Participants will receive their first vitamin B12 injection 1-2 weeks before their
first dose of pemetrexed. They will receive injections every 9 weeks.

- Corticosteroids such as dexamethasone have been shown to help prevent severe skin
rashes associated with pemetrexed. Participants will receive dexamethasone twice daily
starting the day before each pemetrexed infusion continuing until the day after each
infusion.

- On day 1 of each cycle the following will be performed: a physical examination, blood
work, vital signs, assessment of who well the participant is functioning, and
mini-mental examination. On day 8 of each cycle blood work will be performed.

- Research blood work will be obtained (PKs) over the first four days of cycles 1 and 2
(or study participation days 1-4 and 15-18).

- Participants will come to the clinic once a month during the maintenance cycles for a
physical examination, blood work, assessment of how well the participant is
functioning, vital signs and mini-mental examination.

- Tumor assessments by MRI will be done after every 2 cycles during the induction and
consolidation cycles. During the maintenance cycles the MRIs will be repeated every 2
cycles (once every 2 months).

- Collection of cerebral spinal fluid (CSF) for research tests will also likely be
performed, if safe for you, to learn more about how well pemetrexed can cross the
blood-brain barrier. This will be performed by one of two methods 6 and 24 hours after
the pemetrexed is infused on days 1 and 2 of the first two cycles.

- After Alimta is given you will also receive, a white blood cell recruiting material,
Neupogen to avoid suppressing your bone marrow.

Inclusion Criteria:

- Disease state (5 categories of patients with these extremely rare disease are
eligible: 1) Patients intolerant of Methotrexate-must have a diagnosis of B cell
non-Hodgkin's lymphoma 2) Patients unable to receive methotrexate due to lack of drug
availability-must have a diagnosis of B cell non-Hodgkin's lymphoma 3) Patients who
fail to achieve a complete response to initial therapy for primary CNS lymphoma-must
have a diagnosis of B cell non-Hodgkin's lymphoma 4) Recurrent Primary CNS
lymphoma-If in the judgement of the treating physician therapy would be initiated
without a repeat biopsy then the original biopsy with a diagnosis of B cell
non-Hodgkin's lymphoma will suffice 5) Secondary CNS lymphoma-If in the judgement of
the treating physician therapy would be initiated without a repeat biopsy then the
original biopsy with a histologic diagnosis of B cell non-Hodgkin's lymphoma will
suffice.

- Histologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR
cytologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR
immunohistochemical diagnosis of monoclonality (CDF) with or without measurable
intracranial disease OR molecular diagnostic diagnosis of monoclonality CSF) with or
without measurable intracranial disease OR Ocular-patients may have a combination of
histologic confirmation of ocular lymphoma and measurable intracranial tumor.
Slit-lamp examination and vitreal or retinal biopsy will be done to confirm ocular
lymphoma OR neurolymphomatosis-evidence of measurable disease as nerve seeking
lymphoma on MRI imaging with histologic diagnosis at any site.

- Karnofsky score of 60 or greater

- Must be able to undergo MRI scanning

- 18 years of age or older

- Life expectancy of at least 2 months

- Laboratory values as outlined in protocol

- Must be willing to practice an effective method of birth control during participation
in the study whether male or female.

Exclusion Criteria:

- Definitive histologic diagnosis of low grade lymphoma without substantive clinical
suspicion of transformation to an aggressive lymphoma

- Renal dysfunction defined as creatinine clearance < 45 ml/min or serum creatinine >
2mg/dL

- Transaminases > 3 times above the upper limits of the institutional normal

- Acute infection, granulocytopenia or medical condition precluding surgery as judged
by the caring physician and review team

- Pregnant or lactating females

- Patients must not have pre-existing immunosuppression, concurrent immunosuppressive
treatment (with the exception of dexamethasone) or be a transplant recipient

- Patients must not have received prior whole brain irradiation. They can have received
prior focal irradiation

- Prior participation in chemotherapy, cytotoxic therapy, immunotherapy or therapeutic
protocols within 4 weeks fo enrollment. Patients unable to stop NSAIDS or Cox 2
inhibitors for two day before and after treatment as well as the day of treatment

- No other active systemic malignancy with the exception of basal cell carcinoma of the
skin and cervical carcinoma in situ. Patients with a remote history (5 years or more)
of malignancy are eligible for the protocol in the absence of active disease

- Clinically relevant third space fluid collection refractory to drainage

- Patient refusal to participate in the pK study