- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00006246
Busulfan in Treating Children and Adolescents With Refractory CNS Cancer
Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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San Francisco, California, United States, 94143-0128
- UCSF Cancer Center and Cancer Research Institute
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District of Columbia
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Washington, District of Columbia, United States, 20010-2970
- Children's National Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, United States, 15213
- Children's Hospital of Pittsburgh
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Washington
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Seattle, Washington, United States, 98105
- Children's Hospital and Regional Medical Center - Seattle
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
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Maximum tolerated dose of IT administered busulfan
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Serum and CSF pharmacokinetics of IT administered busulfan
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Sri Gururangan, MD, Duke University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- childhood high-grade cerebral astrocytoma
- recurrent childhood large cell lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- recurrent childhood rhabdomyosarcoma
- recurrent childhood acute lymphoblastic leukemia
- childhood infratentorial ependymoma
- recurrent childhood acute myeloid leukemia
- recurrent childhood lymphoblastic lymphoma
- childhood oligodendroglioma
- recurrent childhood supratentorial primitive neuroectodermal tumor
- recurrent childhood cerebellar astrocytoma
- recurrent childhood cerebral astrocytoma
- recurrent childhood ependymoma
- recurrent childhood brain tumor
- recurrent childhood brain stem glioma
- recurrent childhood medulloblastoma
- recurrent childhood visual pathway and hypothalamic glioma
- childhood central nervous system germ cell tumor
- childhood choroid plexus tumor
- childhood grade I meningioma
- childhood grade II meningioma
- childhood grade III meningioma
- recurrent childhood malignant germ cell tumor
- recurrent retinoblastoma
- leptomeningeal metastases
Additional Relevant MeSH Terms
- Nervous System Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Eye Diseases
- Retinal Diseases
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Nerve Tissue
- Eye Diseases, Hereditary
- Eye Neoplasms
- Retinal Neoplasms
- Neoplasms
- Lymphoma
- Neoplasms, Germ Cell and Embryonal
- Leukemia
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Retinoblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Busulfan
Other Study ID Numbers
- CDR0000068178
- PBTC-004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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