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

Phase 1
3 Years
Not Enrolling
Meningitis, Neoplasms

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Trial Information

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

WHAT IS INVOLVED IN THE STUDY? Before participating in this study, there will be a screening


Gemcitabine will be received directly into the cerebrospinal fluid (fluid that circulates
around the brain and spinal cord) through an Ommaya reservoir (or other similar type of
reservoir). An Ommaya reservoir is a surgically implanted catheter that is used to inject
medication or to withdraw cerebrospinal fluid from the fluid chambers in the head.

All patients will be hospitalized overnight following their first dose of gemcitabine. If
the first dose is well tolerated, further doses of gemcitabine will be administered in the
outpatient clinic with close observation for a minimum of 2 hours after administration.

Weeks 1-6 Cohort 1a (first three patients):

Gemcitabine will be given once a week for 6 weeks. Patients may continue therapy if the
disease has not worsened.

Weeks 1-6 (all other patients enrolled on this study):

Gemcitabine will be given twice a week for 6 weeks. Patients may continue therapy if the
disease has not worsened.

Weeks 7-12:

Gemcitabine will be given once a week for 6 weeks.

Weeks 13-29 (approximately):

Gemcitabine will be given twice monthly for 4 months.

Weeks 30-52 (approximately):

Gemcitabine will be given monthly for the duration of the study.

For safety reasons, the first patients treated in the study will receive a low dose of
gemcitabine. If that dose does not cause severe side effects, the next group will receive a
higher dose of gemcitabine than given to the earlier group, or may receive a lower dose if
side effects occur. In addition, the first three patients treated on this study will receive
the gemcitabine once weekly. If this is tolerated, subsequent patients will receive the
medication twice weekly.

Following the first dose of gemcitabine investigators would like to draw special blood and
spinal fluid samples to help learn how much of the drug is in the blood and spinal fluid.
These studies are called pharmacokinetics. A total of 10 samples will be collected. The
blood samples may be collected from an intravenous catheter or a central venous catheter.
The spinal fluid samples may be collected either via Ommaya reservoir or lumbar reservoir.

In addition to intrathecal gemcitabine, the patient may receive other chemotherapy, not
given directly into the fluid surrounding the brain and spine, as recommended by his or her
doctor for the treatment or prevention of cancer outside the lining of the brain and spinal

The maximum length of treatment with gemcitabine is one year. However, at the end of the
study, monthly check-ups are required to monitor the disease and to make sure that any side
effects from the study drug have stopped.

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

- 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

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Asses the toxicity of intrathecally administered gemcitabine in a limited dosage escalation schedule.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Susan Blaney, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:

H10564 IT Gemcitabine



Start Date:

December 2001

Completion Date:

April 2007

Related Keywords:

  • Meningitis
  • Neoplasms
  • Neoplastic meningitis
  • Neoplasms
  • Meningitis
  • Meningeal Carcinomatosis



University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Texas Children's Hospital Houston, Texas  
Seattle Children's Hospital Seattle, Washington  98105
National Cancer Institute Bethesda, Maryland  20892-1922