Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Iodine I 131 metaiodobenzylguanidine, Combination Chemotherapy, and Radiation Therapy in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell or Bone Marrow Transplant for Relapsed or Refractory Neuroblastoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	1 to 29	NCI	NANT-2001-02 NCT00253435

Objectives

Primary

1. 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.

Secondary

1. Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these patients.
2. Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable soft tissue lesions treated with this regimen.
3. Correlate the TSARD with tumor response in patients with measurable residual soft tissue disease treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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 therapy
    • 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)

Prior/Concurrent Therapy:

Biologic therapy

• No prior myeloablative transplantation
  • Prior submyeloablative transplantation allowed at discretion of principal investigator
• More than 3 weeks since prior biologic therapy

Chemotherapy

• 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/m²

Radiotherapy

• See Disease Characteristics
• At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung radiotherapy)
• 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

Other

• 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

Patient Characteristics:

Performance status

• Lansky 60-100%

  OR

• Karnofsky 60-100%

Life expectancy

• At least 2 months

Hematopoietic

• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil count ≥ 750/mm³
• Platelet count ≥ 50,000/mm³ (if no marrow involvement by morphologic exam/no transfusion allowed) (> 20,000/mm³ if metastatic tumor involvement of marrow by morphologic exam/transfusion allowed)

Hepatic

• Bilirubin < 1.3 mg/dL
• SGOT and SGPT < 5 times normal
• Hepatitis B surface antigen negative
• Hepatitis C negative

Renal

• 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)

Cardiovascular

• Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA

  OR

• Fractional shortening ≥ 27% by echocardiogram

Pulmonary

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

Other

• 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

Expected Enrollment

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

Outcomes

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

Event-free survival
Time to progression
Overall survival

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 mL/min)

• 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 thereafter.

Trial Contact Information

Trial Lead Organizations

New Approaches to Neuroblastoma Therapy Consortium

Gregory Yanik, MD, Protocol chair		Ph: 734-936-8785; 800-865-1125 Email: gyanik@umich.edu
Katherine Matthay, MD, Protocol co-chair		Ph: 415-476-0603; 800-888-8664
John Maris, MD, Protocol co-chair		Ph: 215-590-2821 Email: maris@chop.edu

U.S.A.
California
	Los Angeles
	Childrens Hospital Los Angeles
		Judith Villablanca, MD	Ph:  323-361-5654
			Email: jvillablanca@chla.usc.edu
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Clare Twist, MD	Ph:  650-723-5535
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Katherine Matthay, MD	Ph:  415-476-3831
			Email: matthayk@peds.ucsf.edu
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard Katzenstein, MD	Ph:  404-785-0853
Illinois
	Chicago
	University of Chicago Comer Children's Hospital
		Susan Cohn, MD	Ph:  773-703-2571 800-289-6333
			Email: scohn@peds.bsd.uchicago.edu
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Suzanne Shusterman, MD	Ph:  617-632-4901
Michigan
	Ann Arbor
	C.S. Mott Children's Hospital at University of Michigan Medical Center
		Clinical Trials Office - C.S. Mott Children's Hospital	Ph:  1-800-865-1125
New York
	New York
	Morgan Stanley Children's Hospital of New York-Presbyterian
		Julia Glade-Bender, MD	Ph:  212-305-5808
			Email: jg589@columbia.edu
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John Perentesis, MD	Ph:  513-636-6090
			Email: john.perentesis@chmcc.org
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		John Maris, MD	Ph:  215-590-2821
			Email: maris@chop.edu
Texas
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Clinical Trials Office - Cook's Children's Medical Center	Ph:  682-885-2103
	Houston
	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
		Heidi Russell, MD	Ph:  832-822-4277
			Email: hmrussel@txccc.org
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie Park, MD	Ph:  206-987-2106
Wisconsin
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Paul Sondel, MD, PhD	Ph:  608-263-9069
			Email: pmsondel@humonc.wisc.edu
Canada
Ontario
	Toronto
	Hospital for Sick Children
		Sylvain Baruchel, MD	Ph:  416-813-7795

Related Information

PDQ® clinical trial COG-A3973

Registry Information
Official Title		I-Metaiodobenzylguanidine (MIBG) with Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
Trial Start Date		2005-09-28
Trial Completion Date		2010-09-30 (estimated)
Registered in ClinicalTrials.gov		NCT00253435
Date Submitted to PDQ		2005-09-12
Information Last Verified		2009-06-14
NCI Grant/Contract Number		CA81403

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