INCLUSION CRITERIA
AGE
Patients greater than or equal to 3 years of age at study entry.
DIAGNOSIS
Patients must have 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: 1. Leukemia/Lymphoma - CSF cell count greater than 5/microL AND evidence of blast cells on cytospin preparation or by cytology. 2. Solid tumor - Presence of tumor cells on cytospin preparation or cytology OR presence of meningeal disease on MRI scans.
Life Expectancy
Patients must have a life expectancy of at least 6 weeks.
Performance Status
Patients greater than 10 years old should have Karnofsky performance status of greater than or equal to 50 percent and patients less than or equal to 10 years old should have a Lansky performance status of greater than or equal to 50 percent.
Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purposes of the performance score.
Recovery from Prior Therapy
Patients must have recovered from the acute neurotoxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and must be without uncontrolled significant systemic illness (e.g.infection). Patients must not have received any systemic CNS-directed therapy within 3 weeks or craniospinal irradiation within 8 weeks prior to starting treatment on this study. Patients must not have received any intrathecal therapy within 1 week prior to starting treatment on this study.
Hematologic Status
Patients must have a platelet count greater 40,000/mm(3) and Hct greater than 30 percent. Transfusions are allowed to achieve these values, within 48 hours prior to intrathecal gemcitabine treatment. Patients must also have an ANC of greater 1000/microL.
Organ Function
Patients must have adequate liver function, total bilirubin less than 2.0 mg. percent, SGPT less than 5 times upper limits of normal; adequate renal function (serum creatinine less 2 times upper limits of normal for age).
Age Maximum Serum Creatinine
(years)
less than or equal to age 5 0.8 mg/dl
less than age 5 or less than or equal to 10 1.0 mg/dl
less than age 10 or less than or equal to 15 1.2 mg/dl
greater than age 15 1.5 mg/dl
Informed Consent
All patients or their legal guardians (if the patient is less than 18 years of age) must sign a document of informed consent according to their institutional guidelines. When appropriate, patients less than18 years of age will be involved in all discussions in order to obtain verbal assent.
EXCLUSION CRITERIA
Concomitant Therapy:
Patients receiving other therapy (either intrathecal or systemic) designed to treat their leptomeningeal disease are not eligible for this study. 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 [e.g. high-dose methotrexate (greater than 1 g/m2), thiotepa, highdose cytarabine (greater than 1 g/m2), 5-fluorouracil, intravenous 6-mercaptopurine, nitrosoureas, temozolomide, or topotecan], or an agent known to have serious unpredictable CNS side effects. Careful documentation of concurrently administered systemic drugs is required. (Please discuss plans for systemic therapy with the Study Chair or Principal Investigator prior to study entry).
Nuclear Medicine CSF Flow Studies:
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 Technetium 99-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 for this study unless they are shunt-independent and there is evidence that their shunt is nonfunctional (e.g. CSF flow study demonstrating normal flow).
Patients who have leukemia/lymphoma with a concomitant bone marrow relapse are not eligible for this study.
Women of childbearing age must not be pregnant or lactating. (Male and female patients who are fertile must be must be willing to use an effective means of birth control to avoid pregnancy).
Patients must be free of uncontrolled infection except HIV (i.e., AIDS related lymphomatous meningitis).
Patients must NOT be receiving any other investigational agents and must not have received any other investigational agent with-in 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 or requiring local XRT (e.g. optic nerve), are not eligible for this study.
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.
Warren Grant Magnuson Clinical Center (CC)