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
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Drug: buthionine sulfoximine
Drug: melphalan
Procedure: Peripheral blood stem cell infusion
Other: Filgrastim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by New Approaches to Neuroblastoma Therapy Consortium:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: August 2001
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005835

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Illinois
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States, 60637
United States, Massachusetts
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
United States, Texas
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
Investigators
Study Chair: Samuel Volchenboum, MD Comer Children's Hospital, University of Chicago
  More Information

Additional Information:
No publications provided

Responsible Party: New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier: NCT00005835     History of Changes
Other Study ID Numbers: CDR0000067849, P01CA081403, NANT-99-02
Study First Received: June 2, 2000
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New Approaches to Neuroblastoma Therapy Consortium:
regional neuroblastoma
disseminated neuroblastoma
recurrent neuroblastoma
localized unresectable neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Melphalan
Buthionine Sulfoximine
Lenograstim
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Radiation-Protective Agents
Protective Agents
Radiation-Sensitizing Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 29, 2014