Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Intrathecal Gemcitabine in Treating Patients With Cancer and Neoplastic Meningitis

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 3 and over NCI TCCC-H-10564 BCM-H10564, BCM-63667, NCI-V02-1700, NCI-03-C-0032, NCT00074607

Special Category: NCI Web site featured trial

Objectives

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

Entry Criteria

Disease Characteristics:

• Diagnosis of neoplastic meningitis secondary to 1 of the following underlying cancers:
  • Primary leukemia or lymphoma in second or greater relapse
    • Refractory to conventional therapy, including radiotherapy
    • CSF cell count greater than 5/mm³ 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 ventriculoperitoneal or ventriculoatrial shunt unless shunt is nonfunctional and patient is shunt-independent



• 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

Prior/Concurrent Therapy:

Biologic therapy:

• Recovered from prior immunotherapy

Chemotherapy:

• Recovered from prior chemotherapy
• Concurrent chemotherapy for systemic disease or bulk CNS disease allowed provided chemotherapy is 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 an agent 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
• No concurrent CNS radiotherapy
  • Concurrent radiotherapy to extra-CNS sites (e.g., painful bone metastases not in the craniospinal axis) allowed

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

Patient Characteristics:

Age:

• 3 and over

Performance status:

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

Life expectancy:

• At least 6 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm³
• Platelet count greater than 40,000/mm³*
• Hematocrit greater than 30%*

 [Note: *Transfusions allowed]

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGPT less than 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 (i.e., AIDS-related lymphomatous meningitis)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation

Expected Enrollment

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

Outline

This is a nonrandomized, dose-escalation, multicenter study.

• Dose level 1:
  • Cohort 1: Patients receive gemcitabine intrathecally (IT) once weekly in weeks 1-6.
  
  
  
  • Cohort 2: Patients receive gemcitabine IT twice weekly in 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 in weeks 7-12, every other week in weeks 13-28, and then every 4 weeks in 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.

Bernardi RJ, Bomgaars L, Fox E, et al.: Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemother Pharmacol 62 (2): 355-61, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Lisa Bomgaars, MD, Protocol chair		Ph: 832-824-4588 Email: lbomgaars@txccc.org

Registry Information
Official Title		Inthrathecal Gemcitabine Therapy For Neoplatic Meningitis: A Phase I And Pharmcokinetic Study
Trial Start Date		2002-04-09
Registered in ClinicalTrials.gov		NCT00074607
Date Submitted to PDQ		2002-03-29
Information Last Verified		2006-07-06

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