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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier:
NCT00005978
First received: July 5, 2000
Last updated: October 14, 2010
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Biological: filgrastim
Drug: carboplatin
Drug: etoposide
Drug: melphalan
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: iobenguane I 131
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Study Start Date: May 2000
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00005978

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0914
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
United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
Investigators
Study Chair: Katherine K. Matthay, MD Children's Hospital Los Angeles
  More Information

Additional Information:
Publications:
Responsible Party: Katherine Matthay, MD, UCSF
ClinicalTrials.gov Identifier: NCT00005978     History of Changes
Other Study ID Numbers: CDR0000067966, P01CA081403, N99-01
Study First Received: July 5, 2000
Last Updated: October 14, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by New Approaches to Neuroblastoma Therapy Consortium:
localized resectable neuroblastoma
regional neuroblastoma
disseminated neuroblastoma
stage 4S 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
Etoposide
Melphalan
3-Iodobenzylguanidine
Carboplatin
Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiopharmaceuticals

ClinicalTrials.gov processed this record on August 28, 2014