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N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
carboplatin
etoposide
melphalan
autologous bone marrow transplantation
peripheral blood stem cell transplantation
iobenguane I 131
radiation therapy
Sponsored by
New Approaches to Neuroblastoma Therapy Consortium
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring localized resectable neuroblastoma, regional neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, recurrent neuroblastoma, localized unresectable neuroblastoma

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of neuroblastoma as evidenced by one of the following: Histological confirmation Demonstrates clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites High-risk refractory or residual disease Poorly responding disease, meeting 1 of the following criteria: Stable disease or partial response after at least 12 weeks of induction therapy Bone marrow containing greater than 100 tumor cells per 100,000 normal cells after 12 weeks of induction therapy Progressive disease during or after therapy At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan since diagnosis and meets disease status criteria PATIENT CHARACTERISTICS: Age: 1 to 21 (1 to 20 at diagnosis) Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 500/mm^3 Platelet count at least 20,000/mm^3 (transfusion allowed) Hemoglobin at least 8 g/dL (transfusion allowed) Hepatic: Bilirubin normal AST/ALT no greater than 3 times normal No active hepatitis (for HIV-positive patients only) Renal: Glomerular filtration rate or creatinine clearance at least 60 mL/min Creatinine less than 1.5 times normal for age Cardiovascular: Ejection fraction at least 55% OR Fractional shortening at least 30% Pulmonary: No dyspnea at rest or exercise intolerance No requirement for supplemental oxygen No active pneumonia (for HIV-positive patients only) Other: No disease of any major organ system that would preclude study participation No other active health problems (for HIV-positive patients only) No active infections requiring intravenous antivirals, antibiotics, or antifungals Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy and recovered Chemotherapy: At least 3 weeks since prior chemotherapy and recovered No more than 100 mg/m^2 total dose of prior melphalan Endocrine therapy: Not specified Radiotherapy: No prior total body, whole abdominal, or whole liver irradiation No prior therapy with 131 I-MIBG At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to craniospinal or whole lung fields or greater than 50% of bone marrow space) and recovered Surgery: Prior surgical resection allowed Recovered from prior surgery Other: No prior myeloablative therapy Prior submyeloablative therapy with peripheral blood stem cell support allowed No concurrent antiretrovirals for HIV-positive patients Concurrent prolonged antifungal allowed if culture and biopsy negative in suspected residual radiographic lesions No medications that may preclude uptake of 131 I-MIBG for 1 week prior and 2 weeks after administration of study drugs No concurrent hemodialysis

Sites / Locations

  • Children's Hospital Los Angeles
  • Lucile Packard Children's Hospital at Stanford University Medical Center
  • UCSF Comprehensive Cancer Center
  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
  • Children's Memorial Hospital - Chicago
  • Indiana University Cancer Center
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Children's Hospital Boston
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • Texas Children's Cancer Center
  • Children's Hospital and Regional Medical Center - Seattle
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
July 5, 2000
Last Updated
October 14, 2010
Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005978
Brief Title
N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma
Official Title
Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
May 2000 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. PURPOSE: This phase I trial is studying the side effects and best dose of combination chemotherapy when given before stem cell transplant and radiation therapy in treating patients with neuroblastoma that has not responded to previous treatments.
Detailed Description
OBJECTIVES: Determine the maximum tolerated dose and toxic effects of iodine I 131 metaiodobenzylguanidine (131 I-MIBG) plus ablative doses of carboplatin and etoposide administered with fixed-dose melphalan followed by autologous hematopoietic stem cell transplantation in patients with refractory or residual high-risk neuroblastoma. Determine the number of days until blood counts recover in these patients after receiving this treatment regimen. Determine the response rate to this treatment regimen in these patients. Determine the tumor dosimetry of 131 I-MIBG in patients with measurable soft tissue lesions. OUTLINE: This is a dose-escalation study of iodine I 131 metaiodobenzylguanidine (131 I-MIBG), carboplatin, and etoposide. Patients are stratified according to glomerular filtration rate (at least 100 mL/min vs 60-99 mL/min). Patients undergo peripheral blood stem cell harvest or bone marrow harvest at least 2 weeks prior to treatment with 131 I-MIBG. Patients receive 131 I-MIBG IV over 120 minutes on day -21; melphalan IV on days -7 to -5; carboplatin and etoposide IV continuously over 96 hours on days -7 to -4; autologous hematopoietic stem cell transplantation IV over 15-30 minutes on day 0; and filgrastim (G-CSF) subcutaneously or IV starting on day 0 and continuing until blood counts recover. Radiotherapy is administered to the primary tumor site and metastatic sites twice daily for 7 consecutive days within 6 weeks of transplantation or once blood counts have recovered. Cohorts of 3-6 patients receive escalating doses of 131 I-MIBG, carboplatin, and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed at day 84, and then 2 months later if there is a complete response 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 related to study therapy, secondary malignancies, disease status, and survival. PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per stratum) will be accrued for this study within 2-3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
localized resectable neuroblastoma, regional neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, recurrent neuroblastoma, localized unresectable neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
iobenguane I 131
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of neuroblastoma as evidenced by one of the following: Histological confirmation Demonstrates clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites High-risk refractory or residual disease Poorly responding disease, meeting 1 of the following criteria: Stable disease or partial response after at least 12 weeks of induction therapy Bone marrow containing greater than 100 tumor cells per 100,000 normal cells after 12 weeks of induction therapy Progressive disease during or after therapy At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan since diagnosis and meets disease status criteria PATIENT CHARACTERISTICS: Age: 1 to 21 (1 to 20 at diagnosis) Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 500/mm^3 Platelet count at least 20,000/mm^3 (transfusion allowed) Hemoglobin at least 8 g/dL (transfusion allowed) Hepatic: Bilirubin normal AST/ALT no greater than 3 times normal No active hepatitis (for HIV-positive patients only) Renal: Glomerular filtration rate or creatinine clearance at least 60 mL/min Creatinine less than 1.5 times normal for age Cardiovascular: Ejection fraction at least 55% OR Fractional shortening at least 30% Pulmonary: No dyspnea at rest or exercise intolerance No requirement for supplemental oxygen No active pneumonia (for HIV-positive patients only) Other: No disease of any major organ system that would preclude study participation No other active health problems (for HIV-positive patients only) No active infections requiring intravenous antivirals, antibiotics, or antifungals Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy and recovered Chemotherapy: At least 3 weeks since prior chemotherapy and recovered No more than 100 mg/m^2 total dose of prior melphalan Endocrine therapy: Not specified Radiotherapy: No prior total body, whole abdominal, or whole liver irradiation No prior therapy with 131 I-MIBG At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to craniospinal or whole lung fields or greater than 50% of bone marrow space) and recovered Surgery: Prior surgical resection allowed Recovered from prior surgery Other: No prior myeloablative therapy Prior submyeloablative therapy with peripheral blood stem cell support allowed No concurrent antiretrovirals for HIV-positive patients Concurrent prolonged antifungal allowed if culture and biopsy negative in suspected residual radiographic lesions No medications that may preclude uptake of 131 I-MIBG for 1 week prior and 2 weeks after administration of study drugs No concurrent hemodialysis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine K. Matthay, MD
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Lucile Packard Children's Hospital at Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children's Memorial Hospital - Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5289
Country
United States
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0914
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16421427
Citation
Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.
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N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma

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