Brief Title
Busulfan in Treating Children and Adolescents With Refractory CNS Cancer
Official Title
Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die.
PURPOSE: Phase I trial to study the safety of delivering intrathecal busulfan in children and
adolescents who have refractory CNS cancer and to estimate the maximum tolerated dose of this
treatment regimen.
Detailed Description
OBJECTIVES:
- Determine the qualitative and quantitative toxicities of intrathecally administered
busulfan in children and adolescents with refractory CNS malignancies.
- Determine the maximum tolerated dose of this treatment regimen in these patients.
- Determine the cerebrospinal fluid and serum pharmacokinetics of this treatment regimen
in these patients.
- Determine the efficacy of this treatment regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive intrathecal busulfan twice a week, at least 3 days apart, for 2 weeks.
Patients with complete or partial response or stable disease may continue therapy once a week
for 2 weeks, once a week every other week for 2 treatments, and then once a month thereafter
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose limiting toxicities.
Patients are followed every 3 months for the first year, every 6 months for 4 years, and then
annually for 5 years.
PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study over 18-38
months.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
Condition
Brain and Central Nervous System Tumors
Intervention
busulfan
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
28
Start Date
November 2000
Primary Completion Date
May 2003
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed CNS malignancy, including any of the following:
- Primary malignant brain tumor refractory to standard therapy and metastatic to
the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space
- Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor
refractory to conventional therapy
- In second or greater relapse
- CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR
- Evidence of leptomeningeal tumor by MRI
- No concurrent bone marrow disease
- No obstruction or compartmentalization of CSF flow on CSF flow study
PATIENT CHARACTERISTICS:
Age:
- 3 to 21
Performance status:
- Lansky 50-100% (under 10 years)
- Karnofsky 50-100% (10 to 21 years)
Life expectancy:
- Greater than 8 weeks
Hematopoietic:
- Absolute neutrophil count greater than 1,000/mm^3
- Platelet count greater than 75,000/mm^3
Hepatic:
- Bilirubin normal for age
- ALT and AST less than 5 times upper limit of normal (ULN)
- No hepatic disease
Renal:
- Creatinine no greater than 1.5 times ULN OR
- Glomerular filtration rate greater than 70 mL/min
- No renal disease
Cardiovascular:
- No cardiac disease
Pulmonary:
- No pulmonary disease
Other:
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
- At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and
recovered
- Evidence of subsequent disease progression
- Concurrent systemic chemotherapy allowed for recurrent disease after first course of
treatment except for the following:
- Chemotherapy targeted at leptomeningeal disease
- Other phase I agent
- Any agent that significantly penetrates the CSF (e.g., high dose methotrexate
greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV
mercaptopurine, nitrosoureas, or topotecan)
- Any agent that causes serious unpredictable CNS side effects
Endocrine therapy:
- Prior dexamethasone allowed with decreasing or stable dose at least one week before
study
- Concurrent dexamethasone or prednisone with chemotherapy regimen allowed
Radiotherapy:
- At least 1 week since prior focal irradiation to the brain or spine
- At least 8 weeks since prior craniospinal irradiation
- No concurrent cranial or craniospinal irradiation
Surgery:
- Not specified
Other:
- No other concurrent intrathecal or systemic therapy for leptomeningeal disease
Gender
All
Ages
3 Years - 21 Years
Accepts Healthy Volunteers
No
Contacts
Sri Gururangan, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00006246
Organization ID
CDR0000068178
Secondary IDs
PBTC-004
Study Sponsor
Pediatric Brain Tumor Consortium
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Sri Gururangan, MD, Study Chair, Duke University
Verification Date
October 2009