RATIONALE: Giving gemcitabine intrathecally may be an effective treatment for neoplastic meningitis.

PURPOSE: Phase I trial to study the effectiveness of intrathecal gemcitabine in treating patients who have cancer and neoplastic meningitis.

Condition	Treatment or Intervention	Phase
leptomeningeal metastases	Drug: gemcitabine  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of intrathecal gemcitabine in patients with neoplastic meningitis.
• Determine the qualitative and quantitative toxicity of this drug in these patients.
• Determine the plasma and CSF pharmacokinetics of this drug in these patients.
• Determine the response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

• Cohort 1: Patients receive gemcitabine intrathecally (IT) once weekly on weeks 1-6.
• Cohort 2: Patients receive gemcitabine IT twice weekly on weeks 1-6.
• Dose levels 2-6: Patients receive gemcitabine as in cohort 2 of dose level 1. All patients with stable or responding disease receive gemcitabine IT once weekly on weeks 7-12, every other week on weeks 13-28, and then every 4 weeks on weeks 29-52.

Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for 3 months and then every 3-4 months for up to 1 year.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study within 2-3 years.

Ages Eligible for Study:  3 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of neoplastic meningitis secondary to an underlying cancer
• Primary leukemia or lymphoma in second or greater relapse
• Refractory to conventional therapy, including radiotherapy
• CSF cell count greater than 5/mm^3 AND evidence of blast cells on cytospin preparation or by cytology
• Primary solid tumor
• Presence of tumor cells on cytospin preparation or cytology OR presence of meningeal disease on MRI scan
• No concurrent bone marrow relapse with leukemia or lymphoma
• No evidence of obstructive hydrocephalus or compartmentalization of CSF flow as documented by radioisotope flow study
• No impending spinal cord compression, CNS involvement (e.g., optic nerve) requiring local radiotherapy, or isolated bulky ventricular or leptomeningeal lesions

PATIENT CHARACTERISTICS: Age:

• 3 and over

Performance status:

• Karnofsky 50-100% (over 10 years)
• Lansky 50-100% (10 years and under)

Life expectancy:

• At least 6 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 40,000/mm^3 (transfusions allowed)

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGPT less than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine less than 2 times ULN
• No clinically significant abnormalities of serum electrolytes, including calcium, magnesium, and phosphorus

Other:

• No other uncontrolled significant systemic illness
• No uncontrolled infection except HIV
• No ventriculoperitoneal or ventriculoatrial shunt unless shunt is nonfunctional and patient is shunt-independent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Recovered from prior immunotherapy

Chemotherapy:

• Recovered from prior chemotherapy
• Concurrent chemotherapy for systemic disease or bulk CNS disease allowed if not a phase I agent, an agent that significantly penetrates the CSF (e.g., high-dose methotrexate, thiotepa, high-dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, temozolomide, or topotecan), or agents with serious unpredictable CNS side effects

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 8 weeks since prior craniospinal or cranial irradiation and recovered
• Recovered from prior radiotherapy
• No concurrent CNS radiotherapy

Surgery:

• Not specified

Other:

• At least 1 week since prior intrathecal therapy
• At least 2 weeks since prior investigational agents
• At least 3 weeks since prior systemic CNS-directed therapy
• No other concurrent systemic or intrathecal therapy for leptomeningeal disease
• No other concurrent investigational agents

Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Pennsylvania
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-1863,  United States; Recruiting
Texas
      Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston,  Texas,  77030-2399,  United States; Recruiting

Study chairs or principal investigators

Susan M. Blaney, MD,  Study Chair,  Texas Children's Cancer Center   
Lisa Bomgaars, MD,  Texas Children's Cancer Center   

Study ID Numbers:  CDR0000069356; TCCC-H-10564; BCM-H10564; BCM-63667; NCI-V02-1700; NCT00039143
Record last reviewed:  August 2004
Last Updated:  April 5, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039143
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08