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I-MIBG Escalating Dose Rapid Sequence Double Infusion Followed By Autologous Stem Cell Infusion For Refractory Neuroblastoma

Phase 1
1 Year
30 Years
Not Enrolling

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Trial Information

I-MIBG Escalating Dose Rapid Sequence Double Infusion Followed By Autologous Stem Cell Infusion For Refractory Neuroblastoma



- Determine the maximum tolerated red marrow radiation dose delivered and associated
toxic effects of escalating activity of iodine I 131 metaiodobenzylguanidine
(^131I-MIBG) followed by autologous hematopoietic stem cell transplantation in patients
with refractory neuroblastoma.

- Determine the number of days after stem cell transplantation to achieve absolute
neutrophil count ≥ 500/mm^3 for 3 days and platelet count ≥ 20,000/mm^3 for 3 days
(without transfusions) in patients treated with this regimen.


- Determine the response rate in patients treated with this regimen, based on lesions
measurable by CT or MRI at study entry, patients with ^131I-MIBG scan-positive lesions
only, and patients with minimal residual tumor in bone marrow who have complete
response by immunocytology and morphology.

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

- Correlate, if possible, TP53 mutations with response in patients with accessible bone
marrow tumor treated with ^131I-MIBG.

OUTLINE: This is a dose-escalation, multicenter study.

- Iodine I 131 metaiodobenzylguanidine (131I-MIBG) therapy: Patients receive^131I-MIBG IV
over 2 hours on days 0 and 14.

Cohorts of 3-6 patients receive escalating doses of ^131I-MIBG 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.

- Stem cell transplantation therapy: Patients undergo autologous peripheral blood stem
cell transplantation on day 28. Patients receive filgrastim (G-CSF) IV over 1 hour OR
subcutaneously daily beginning on day 28 and continuing until blood counts recover.

Patients are followed every 3 months for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for this study within 2 years.

Inclusion Criteria


- Diagnosis of neuroblastoma

- Confirmed by at least 1 of the following methods:

- Histology

- Clumps of tumor cells in bone marrow with elevated urinary catecholamine

- High-risk disease

- Poor response to induction therapy OR relapse defined by any of the

- No response, stable disease, or mixed response after a minimum of 3
prior courses of chemotherapy

- More than 100 tumor cells per 10^5 nucleated cells on bone marrow
immunocytology after at least 3 prior courses of chemotherapy

- Progressive disease at any time during or after therapy

- Patients with massive bone marrow invasion (more than 50% replacement
of bone marrow by tumor cells) are allowed

- Must have positive iodine I 131 metaiodobenzylguanidine (^131I-MIBG) within the past
6 weeks or subsequent to any other prior antitumor therapy delivered within the past
6 weeks

- Must meet the following criteria for minimum number of autologous stem cells:

- Unpurged peripheral blood stem cells (PBSC)

- Minimum of 1,500,000/mm^3 CD34-positive cells/kg

- Collected products must have < 1 tumor cell/100,000 normal cells by

- PBSC purged with immunomagnetic beads

- Minimum of 1,000,000/mm^3 viable CD34-positive cells/kg

- Collected products must have < 1 tumor cell/100,000 normal cells by

- CD34-positive selected PBSC products are not allowed

- Patients who had PBSC collected previously with no immunocytological testing
available may use those products provided bone marrow is tumor free by bilateral
bone marrow aspirate AND biopsy for morphology is performed within 4 weeks
before PBSC collection

- Patients with no tumor involvement in bone marrow at diagnosis and PBSC
collection before any disease progression do not require documentation of
negative bone marrow morphology



- 1 to 30

Performance status

- ECOG 0-2

Life expectancy

- Less than 1 year


- Absolute neutrophil count ≥ 500/mm^3

- Platelet count ≥ 50,000/mm^3 (without transfusion)

- Hemoglobin ≥ 8 g/dL (transfusion allowed)


- AST and ALT ≤ 5 times normal

- Bilirubin < 2 times normal


- Creatinine ≤ 1.5 mg/dL

- Glomerular filtration rate OR 12-hour creatinine clearance ≥ 60 mL/min/1.73m^2


- Ejection fraction ≥ 55% by echocardiogram or MUGA OR

- Fractional shortening ≥ 30% OR above lower limit of normal by echocardiogram


- Normal lung function

- No dyspnea at rest

- No exercise intolerance

- No oxygen requirement


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to cooperate physically and psychologically with radiation isolation

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

- No active infection requiring antivirals, antibiotics, or antifungals

- No weight that would require exceeding a maximum total allowable dose of ^131I-MIBG


Biologic therapy

- At least 2 weeks since prior biologic or other non-myelosuppressive therapy


- See Disease Characteristics

- At least 2 weeks since prior chemotherapy

- More than 3 months since prior myeloablative therapy

Endocrine therapy

- Not specified


- See Disease Characteristics

- At least 6 months since prior craniospinal, total abdominal, or whole lung

- At least 2 weeks since prior radiotherapy to any site

- No prior total body irradiation

- No prior radiotherapy to > 25% of bone marrow

- No prior ^131I-MIBG


- Not specified


- Recovered from all prior therapy

- Concurrent antifungal therapy allowed provided culture and biopsy are negative in
suspected radiographic lesions

- Prior re-induction therapy for recurrent tumor allowed

- No concurrent antiretroviral therapy for HIV-positive patients

- No concurrent hemodialysis

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Katherine K. Matthay, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • Neuroblastoma



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Indiana University Cancer Center Indianapolis, Indiana  46202-5265
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
Children's Hospital Los Angeles Los Angeles, California  90027-0700
UCSF Comprehensive Cancer Center San Francisco, California  94115
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Children's Hospital Boston Boston, Massachusetts  02115