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I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

Phase 2
1 Year
29 Years
Open (Enrolling)

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Trial Information

I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma



- Determine the response rate in patients with relapsed or refractory neuroblastoma
treated with iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination
chemotherapy comprising carboplatin, etoposide, and melphalan followed by autologous
bone marrow or peripheral blood stem cell transplantation and radiotherapy.


- Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these

- Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable
soft tissue lesions treated with this regimen.

- Correlate the TSARD with tumor response in patients with measurable residual soft
tissue disease treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (poor-risk
group [mixed or no response to induction therapy or progression during or after induction
therapy] vs good-risk group [partial response after 4 courses of induction therapy]) and
kidney function at study entry (glomerular filtration rate [GFR] ≥ 100 mL/min vs GFR 60-99

- Stem cell harvest: Patients undergo a peripheral blood stem cell harvest or bone marrow
harvest provided they have an adequate number of cells available. At least 2 weeks
later, patients proceed to iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and
combination chemotherapy.

- 131I-MIBG and combination chemotherapy: Patients receive ^131I-MIBG IV over 2 hours on
day -21, carboplatin IV continuously on days -7 to -4, etoposide IV continuously on
days -7 to -4, and melphalan IV over 1 hour on days -7 to -5.

- Stem cell infusion and filgrastim (G-CSF): Three days after completion of chemotherapy,
patients undergo transplantation of either stem cells or bone marrow on day 0. Patients
also receive G-CSF subcutaneously or IV over 1 hour once daily beginning on day 0 and
continuing until blood counts return to normal.

- Radiotherapy: Once blood counts return to normal, patients undergo radiotherapy to
primary and metastatic sites that have not received previous irradiation over 12 days
beginning after day 42.

After completion of study treatment, patients are followed for 2 years and then periodically

PROJECTED ACCRUAL: Approximately 50 patients (40 low-risk patients and 8-10 high-risk
patients) will be accrued for this study.

Inclusion Criteria


- Diagnosis of relapsed or refractory neuroblastoma

- Histologically confirmed and/or demonstration of tumor cells in bone marrow with
elevated urinary catecholamine metabolites

- High-risk neuroblastoma must meet one of the following:

- Progressive disease prior to or after completion of induction therapy

- Mixed response or no response after completion of 4 courses of induction

- Partial response after 4 courses of induction therapy allowed provided no
prior participation in COG-A3973 or other phase III COG trials

- Measurable disease, defined as at least one metaiodobenzylguanidine (MIBG)-avid
target lesion determined by diagnostic MIBG scan within 6 weeks of study entry (tumor
sites that have received local irradiation within 3 months of study entry are not
considered target lesions)


Performance status

- Lansky 60-100% OR

- Karnofsky 60-100%

Life expectancy

- At least 2 months


- Hemoglobin ≥ 10 g/dL

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 50,000/mm^3 (if no marrow involvement by morphologic exam/no
transfusion allowed) (> 20,000/mm^3 if metastatic tumor involvement of marrow by
morphologic exam/transfusion allowed)


- Bilirubin < 1.3 mg/dL

- SGOT and SGPT < 5 times normal

- Hepatitis B surface antigen negative

- Hepatitis C negative


- Glomerular filtration rate or creatinine clearance ≥ 60 ml/min

- Creatinine ≤ 1.5 times normal for age as follows:

- 0.8 mg/dL (for patients ≤ 5 years of age)

- 1.0 mg/dL (for patients 6 to 10 years of age)

- 1.2 mg/dL (for patients 11 to 15 years of age)

- 1.5 mg/dL (for patients > 15 years of age)


- Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR

- Fractional shortening ≥ 27% by echocardiogram


- Normal lung function defined as no dyspnea at rest and no oxygen requirement OR
measured oxygen saturation > 93% on room air


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No disease of any major organ system that would preclude study compliance

- No concurrent hemodialysis

- No active infection requiring IV antivirals, antibiotics, or antifungals (patients on
antifungal therapy are eligible provided they are culture- and biopsy-negative in
suspected residual radiographic lesions)

- Patient weight within limits to receive ≤ maximum total allowable dose of ^131I-MIBG


Biologic therapy

- No prior myeloablative transplantation

- Prior submyeloablative transplantation allowed at discretion of principal

- More than 3 weeks since prior biologic therapy


- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for mitomycin C
or nitrosoureas)

- No prior melphalan therapy with a total dose of > 100 mg/m^2


- See Disease Characteristics

- At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung

- No prior total body irradiation

- No prior iodine I 131 MIBG (^131I-MIBG)

- No prior total abdominal or whole liver radiotherapy

- No prior local radiotherapy, including any of the following:

- 1200 cGy to more than 33% of both kidneys (patient must have at least one kidney
that has not exceeded the dose/volume of radiation listed)

- 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver


- Recovered from all prior therapy

- No medications with a potential interference of ^131I-MIBG uptake 1 week before and 2
weeks after completion of ^131I-MIBG

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response (complete response, very good partial response, and partial response) at 60-days post stem cell infusion

Safety Issue:


Principal Investigator

Gregory Yanik, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Michigan Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • Neuroblastoma



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Cook Children's Medical Center - Fort Worth Fort Worth, Texas  76104
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Childrens Hospital Los Angeles Los Angeles, California  90027
Lucile Packard Children's Hospital at Stanford University Medical Center Palo Alto, California  95798
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Atlanta, Georgia  30322
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Boston, Massachusetts  02115
C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor, Michigan  48109-0286
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital Houston, Texas  77030-2399
University of Chicago Comer Children's Hospital Chicago, Illinois  60637
Morgan Stanley Children's Hospital of New York-Presbyterian New York, New York  10032