Intrathecal Gemcitabine Therapy for Neoplastic Meningitis: A Phase I and Pharmacokinetic Study

Inclusion Criteria:

- at least 3 years of age.

- Neoplastic meningitis secondary to an underlying leukemia/lymphoma or a solid tumor
(including primary CNS tumors or carcinomas of unknown primary site) for which there
is no conventional therapy. Patients with CNS leukemia/lymphoma must be refractory
to conventional therapy, including XRT (i.e. 2nd or greater relapse). Neoplastic
meningitis is defined as follows:

- Leukemia/Lymphoma: CSF cell count > 5 uL AND evidence of blast cells on cytospin
preparation or by cytology.

- Solid tumor: Presence of tumor cells on cytospin preparation or cytology OR
presence of meningeal disease on MRI scans.

- Life expectancy of at least 6 weeks.

- Patients > 10 years old: Karnofsky performance status of >/= 50%. Patients years old: Lansky performance status of >/= 50%.

- Must have recovered from the acute neurotoxic effects of all prior chemo, immuno, or
radiotherapy and must be without uncontrolled significant systemic illness (e.g.
infection). Must not have received any systemic CNS-directed therapy within 3 weeks
or craniospinal irradiation within 8 weeks prior to starting treatment on study.
Must not have received any intrathecal therapy within 1 week prior to starting
treatment on study.

- Must have a platelet count >40,000/uL and HCT >30% and an ANC of > 1000/uL.

- Must have adequate liver function, total bilirubin < 2.0 mg, SGPT < 5 times upper
limits of normal; adequate renal function (serum creatinine < 2 times upper limits of
normal for age).

- Patients must have or be willing to have an intraventricular access device such as an
Ommaya reservoir.

Exclusion Criteria:

- Patients receiving other therapy (either intrathecal or systemic) designed to treat
their leptomeningeal disease. However, patients receiving concomitant chemotherapy
to control systemic disease or bulk CNS disease will be eligible, provided that the
systemic chemotherapy is not a phase I agent, an agent that significantly penetrates
the CSF, or an agent known to have serious unpredictable CNS side effects.

- Nuclear Medicine CSF flow studies are required within the 2 weeks prior to study
entry for all solid tumor patients. In leukemia/lymphoma patients a CSF flow study
is only required if CSF analysis or an MRI suggests that there is a blockage to CSF
flow. Patients with clinical evidence of obstructive hydrocephalus are not eligible
for this protocol. Nor are patients with compartmentalization of CSF flow as
documented by radioisotope Indium111 or Technetium99-DTPA flow eligible for this
protocol. If a CSF flow block or compartmentalization is demonstrated, focal
radiotherapy to the site of the block to restore flow followed by a repeat CSF flow
study demonstrating clearing of the blockage is required for the patient to be
eligible for the study.

- Patients must not have clinically significant abnormalities of serum electrolytes,
including calcium, magnesium, and phosphorus.

- Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt are not
eligible unless they are shunt-independent and there is evidence that their shunt is
nonfunctional

- Patients who have leukemia/lymphoma with a concomitant bone marrow relapse.

- Women of childbearing age must not be pregnant or lactating. (Male and female
patients who are fertile must be willing to use an effective means of birth control
to avoid pregnancy.)

- Must be free of uncontrolled infection except HIV (i.e., AIDS-related lymphomatous
meningitis).

- Must NOT be receiving any other investigational agents and must not have received any
other investigational agent within 14 days prior to study treatment. The 14-day
period should be extended if the investigational agent is known to have delayed
toxicity.

- Patients with impending spinal cord compression, CNS involvement requiring local XRT
(e.g. optic nerve), or isolated bulky ventricular or leptomeningeal based lesions are
not eligible.

- Concomitant CNS radiation therapy is not permitted. (Patients are not permitted to
receive radiation to any port that encompasses any part of the brain or spine while
on study.) Patients may receive radiation therapy to extra-CNS sites, e.g. painful
bone metastases not in the craniospinal axis.