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Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

Primary Purpose

Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
busulfan
Sponsored by
Pediatric Brain Tumor Consortium
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCSF Cancer Center and Cancer Research Institute
  • Children's National Medical Center
  • Dana-Farber Cancer Institute
  • Duke Comprehensive Cancer Center
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Baylor College of Medicine
  • Children's Hospital and Regional Medical Center - Seattle

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
September 11, 2000
Last Updated
October 6, 2009
Sponsor
Pediatric Brain Tumor Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006246
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2009
Overall Recruitment Status
Completed
Study Start Date
November 2000 (undefined)
Primary Completion Date
May 2003 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Pediatric Brain Tumor Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
busulfan
Primary Outcome Measure Information:
Title
Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
Title
Maximum tolerated dose of IT administered busulfan
Title
Serum and CSF pharmacokinetics of IT administered busulfan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sri Gururangan, MD
Organizational Affiliation
Duke University
Official's Role
Study Chair
Facility Information:
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4318
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16533779
Citation
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.
Results Reference
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Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

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