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Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 3 Years - 21 Years
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00006246
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Pediatric Brain Tumor Consortium
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Sri Gururangan, MD
Principal Investigator Affiliation Duke University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Leukemia, Lymphoma, Metastatic Cancer, Retinoblastoma, Sarcoma
Additional Details

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

San Francisco, California

Status

Address

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94143-0128

Children's National Medical Center, Washington, District of Columbia

Status

Address

Children's National Medical Center

Washington, District of Columbia, 20010-2970

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

Duke Comprehensive Cancer Center, Durham, North Carolina

Status

Address

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Status

Address

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania

Status

Address

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213

Baylor College of Medicine, Houston, Texas

Status

Address

Baylor College of Medicine

Houston, Texas, 77030

Seattle, Washington

Status

Address

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105