N99-02: Melphalan and Buthionine Sulfoximine Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Children With Resistant or Recurrent Neuroblastoma
Information source: New Approaches to Neuroblastoma Therapy Consortium
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neuroblastoma
Intervention: buthionine sulfoximine (Drug); melphalan (Drug); Peripheral blood stem cell infusion (Procedure); Filgrastim (Other)
Phase: Phase 1
Sponsored by: New Approaches to Neuroblastoma Therapy Consortium
Official(s) and/or principal investigator(s):
Samuel Volchenboum, MD, Study Chair, Affiliation: Comer Children's Hospital, University of Chicago
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell
transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill
more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of melphalan and buthionine sulfoximine
followed by bone marrow or peripheral stem cell transplantation in treating children who
have resistant or recurrent neuroblastoma.
Official title: Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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.
To determine the pharmacokinetics (PK) of BSO and L-PAM in pediatric patients.
To determine the response rate of recurrent high risk neuroblastoma to BSO/LPAM within the confines of a phase I study.
To determine the glutathione content of peripheral blood leucocytes in patients receiving BSO and L-PAM.
To determine the number of days to ANC =/> 500 for three days and platelets =/> 20,000 for three days (without transfusion) for this regimen.
- 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.
Minimum age: N/A.
Maximum age: 30 Years.
- 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.
- 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.
Locations and Contacts
Childrens Hospital Los Angeles, Los Angeles, California 90027-0700, United States; Recruiting
Araz Marachelian, MD, Phone: 323-361-5687, Email: email@example.com
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94143, United States; Recruiting
Katherine K. Matthay, MD, Phone: 415-476-3831, Email: matthayK@peds.ucsf.edu
University of Chicago Comer Children's Hospital, Chicago, Illinois 60637, United States; Recruiting
Susan L. Cohn, MD, Phone: 773-702-2571, Email: firstname.lastname@example.org
Childrens Hospital Boston, Dana-Farber Cancer Institute., Boston, Massachusetts 02115, United States; Recruiting
Suzanne - Shusterman, MD, Phone: 617-632-3725, Email: email@example.com
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States; Recruiting
Brian Weiss, MD, Phone: 513-636-9863, Email: firstname.lastname@example.org
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; Recruiting
Sylvain Baruchel, MD, Phone: 416-813-7795, Email: email@example.com
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, United States; Recruiting
Yael Mosse, MD, Phone: 215-590-0965, Email: firstname.lastname@example.org
CHU Sainte Justine, Montreal, Quebec H3T 1C5, Canada; Recruiting
Pierre Teira, MD, Phone: 514-345-4870, Email: email@example.com
Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States; Recruiting
Clinical Trials Office - Cook's Children's Medical Center, Phone: 682-885-2103
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States; Recruiting
Julie R. Park, MD, Phone: 206-987-1947, Email: Julie.firstname.lastname@example.org
Clinical trial summary from the National Cancer Institute's PDQ® database
N99-02 Information on NANT.org
Starting date: August 2001
Last updated: April 26, 2012