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Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)

Phase 1
30 Years
Open (Enrolling)

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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)


- 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

- 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:


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:


Principal Investigator

Samuel Volchenboum, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Comer Children's Hospital, University of Chicago


United States: Food and Drug Administration

Study ID:




Start Date:

August 2001

Completion Date:

June 2014

Related Keywords:

  • Neuroblastoma
  • regional neuroblastoma
  • disseminated neuroblastoma
  • recurrent neuroblastoma
  • localized unresectable neuroblastoma
  • Neuroblastoma



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