Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

NCT00006246 | Completed Phase 1 DMC

• 2 other identifiers: CDR0000068178PBTC-004
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Keywords

recurrent childhood acute lymphoblastic leukemia; childhood infratentorial ependymoma; recurrent childhood rhabdomyosarcoma; recurrent childhood brain tumor; recurrent retinoblastoma; recurrent childhood lymphoblastic lymphoma; childhood central nervous system germ cell tumor; recurrent childhood acute myeloid leukemia; recurrent/refractory childhood Hodgkin lymphoma; leptomeningeal metastases; childhood high-grade cerebral astrocytoma; childhood oligodendroglioma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood large cell lymphoma; recurrent childhood brain stem glioma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood medulloblastoma; recurrent childhood visual pathway and hypothalamic glioma; recurrent childhood ependymoma; recurrent childhood malignant germ cell tumor

Outcome Measures

Primary Outcomes (3)

• Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies

• Maximum tolerated dose of IT administered busulfan

• Serum and CSF pharmacokinetics of IT administered busulfan

Interventions

busulfan DRUG

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94143-0128, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, Bomgaars L, Blaney SM, Kun LE, Boyett JM. Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC-004). Clin Cancer Res. 2006 Mar 1;12(5):1540-6. doi: 10.1158/1078-0432.CCR-05-2094.

  PMID: 16533779 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Leukemia; Lymphoma; Neoplasm Metastasis; Retinoblastoma; Sarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Meningeal Carcinomatosis; Astrocytoma; Oligodendroglioma; Choroid Plexus Neoplasms; Dendritic Cell Sarcoma, Interdigitating; Medulloblastoma; Optic Nerve Glioma; Familial ependymoma

Interventions

Busulfan

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Neoplasms, Connective and Soft Tissue; Leukemia, Lymphoid; Disease Attributes; Meningeal Neoplasms; Glioma; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Neuroectodermal Tumors, Primitive; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Sri Gururangan, MD

  Duke University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: January 27, 2003
• Study Start: November 1, 2000
• Primary Completion: May 1, 2003
• Last Updated: October 7, 2009

Record last verified: 2009-10

Locations

US (8)