N99-02: Melphalan and Buthionine Sulfoximine Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Children With Resistant or Recurrent Neuroblastoma (BSO)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier:
NCT00005835
First received: June 2, 2000
Last updated: April 3, 2014
Last verified: April 2014

June 2, 2000
April 3, 2014
August 2001
December 2014   (final data collection date for primary 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. [ Time Frame: Within 4 weeks of completion of BSO/L-PAM therapy ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00005835 on ClinicalTrials.gov Archive Site
  • To determine the pharmacokinetics (PK) of BSO and L-PAM in pediatric patients. [ Time Frame: For BSO: just before start of therapy to 8 hours post end of 72 infusion. For L-PAM : just before start of 2nd dose to 4 hours post. ] [ Designated as safety issue: Yes ]
    Collection of blood samples for PK studies is optional and not required for study entry.
  • To determine the response rate of recurrent high risk neuroblastoma to BSO/LPAM within the confines of a phase I study. [ Time Frame: 84 days after completion of therapy with BSO/L-PAM and Stem cell re-infusion. ] [ Designated as safety issue: No ]
  • To determine the glutathione content of peripheral blood leucocytes in patients receiving BSO and L-PAM. [ Time Frame: For BSO: just before start of therapy to 8 hours post end of 72 infusion. For L-PAM : just before start of 2nd dose to 4 hours post. ] [ Designated as safety issue: No ]
    Collection of blood samples for biologic studies is optional and not required for study entry.
  • To determine the number of days to ANC =/> 500 for three days and platelets =/> 20,000 for three days (without transfusion) for this regimen. [ Time Frame: Maximum 56 days after completion of therapy with BSO/L-PAM and Stem cell re-infusion. ] [ Designated as safety issue: Yes ]
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N99-02: Melphalan and Buthionine Sulfoximine Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Children With Resistant or Recurrent Neuroblastoma
Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neuroblastoma
  • Drug: buthionine sulfoximine
    Dose fixed at a bolus of 3 gm/M2 given over 30 minutes followed by a continuous infusion of 1 gm/M2/hour for 72 hours (total 72.5 hours).Total daily infusion dose (minus the initial bolus)will be 24 gm/m2/day.
    Other Name: BSO
  • Drug: melphalan
    The dose level of melphalan will be assigned at study entry onto protocol. There will be 6 dose levels ranging from 20mg/m2/day x 2 days (dose level 1a) to 62.5 mg/m2/day x 2 days (dose level 6a). The starting dose level will be 1a, with a decrease to level 0a (15mg/m2/day x2 days) if there is unacceptable toxicity.
    Other Name: L-PAM
  • Procedure: Peripheral blood stem cell infusion
    Stem cells will be infused intravenously on day 0 , 24 hours after BSO continuous infusion is completed.Infused within 1.5 hours of thawing via a central venous catheter over 15-30 minutes.
    Other Names:
    • PBSCT
    • Autologous Bone marrow Transplant
    • ABMT
  • Other: Filgrastim
    5 microgram/kg/day , subcutaneous or intravenous, given daily beginning day 0. First dose to begin 4 hours after completion of stem cell infusion and then to continue till ANC >/= 1500 mm3 for three consecutive days.
    Other Name: G-CSF
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
December 2014
December 2014   (final data collection date for primary outcome measure)

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.
Both
up to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00005835
CDR0000067849, P01CA081403, NANT-99-02
Yes
New Approaches to Neuroblastoma Therapy Consortium
New Approaches to Neuroblastoma Therapy Consortium
National Cancer Institute (NCI)
Study Chair: Samuel Volchenboum, MD Comer Children's Hospital, University of Chicago
New Approaches to Neuroblastoma Therapy Consortium
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP