Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)
N/A
30 Years
Both
Neuroblastoma
Trial Information
Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)
OBJECTIVES:
- Determine the maximum tolerated dose of melphalan when combined with buthionine
sulfoximine and followed by autologous bone marrow or peripheral blood stem cell
support in children with resistant or recurrent high-risk neuroblastoma.
- Assess the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the response rate of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of melphalan.
Patients receive buthionine sulfoximine IV as a bolus over 30 minutes followed by a 72-hour
continuous infusion beginning on day -4; melphalan IV over 15 minutes on days -3 and -2;
autologous peripheral blood stem cells or bone marrow IV over 15-30 minutes on day 0; and
filgrastim (G-CSF) subcutaneously or IV once daily beginning on day 0 and continuing until
blood counts recover.
Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Patients are followed at 84 days and then 2 months later if there is a complete and/or
partial response. Patients who continue therapy on other protocols are followed before
starting the new therapy. All patients are followed for life for any delayed toxic effects
to protocol therapy and secondary malignancies.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2-3 years.
Inclusion Criteria:
- Patients have relapsed neuroblastoma and must have exhausted all other options for
treatment before they can be considered for treatment on this study.
- Relapsed patients who are greater than 6 months since having a stem cell transplant
can enter on this study.
- Patients must have stem cells collected and stored before starting treatment.
- Patients must have a double lumen central venous line in place.
- Patients must have adequate kidney and liver function measured by blood tests and
test of renal function (creatinine clearance or glomerular filtration rate (GFR)).
- Patients must have normal heart and lung function measured by lack of physical
evidence or clinical history of difficulties breathing and tests of cardiac function
(Echocardiogram or MUGA evaluation).
- Patients must have an essentially normal neurological exam.
- Patients must have one entire kidney that has not had any radiation at treatment
doses. (Xrays and scans are ok).
- Patients must have recovered from the effects of any prior treatment for their tumor.
Exclusion Criteria:
- They have had any radiation therapy to the brain.
- They have known history of or current tumor found in the brain or surrounding
tissues.
- They have a history of seizures.
- They have a history of changes in a test of kidney function with antibiotic use in
the 6 months immediately before entering on this study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the maximum tolerated dose(MTD) and the toxicities of Melphalan (L-PAM) escalated in the presence of Buthionine sulphoxamine (BSO) and followed by autologous stem cells rescue for pediatric patients with high-risk neuroblastoma.
Outcome Time Frame:
Within 4 weeks of completion of BSO/L-PAM therapy
Safety Issue:
Yes
Principal Investigator
Samuel Volchenboum, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Comer Children's Hospital, University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000067849
NCT ID:
NCT00005835
Start Date:
August 2001
Completion Date:
June 2014
Related Keywords:
- Neuroblastoma
- regional neuroblastoma
- disseminated neuroblastoma
- recurrent neuroblastoma
- localized unresectable neuroblastoma
- Neuroblastoma
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Childrens Hospital Los Angeles | Los Angeles, California 90027 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
| University of Chicago Comer Children's Hospital | Chicago, Illinois 60637 |
| Childrens Hospital Boston, Dana-Farber Cancer Institute. | Boston, Massachusetts 02115 |
