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N2000-01: Double Infusion of Iodine I 131 Metaiodobenzylguanidine Followed by Autologous Stem Cell Transplantation

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
autologous bone marrow transplantation
peripheral blood stem cell transplantation
iobenguane I 131
Sponsored by
Children's Hospital Los Angeles
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring recurrent neuroblastoma

Eligibility Criteria

1 Year - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of neuroblastoma Confirmed by at least 1 of the following methods: Histology Clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites High-risk disease Poor response to induction therapy OR relapse defined by any of the following: 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 immunocytology 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 immunocytology 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 PATIENT CHARACTERISTICS: Age 1 to 30 Performance status ECOG 0-2 Life expectancy Less than 1 year Hematopoietic Absolute neutrophil count ≥ 500/mm^3 Platelet count ≥ 50,000/mm^3 (without transfusion) Hemoglobin ≥ 8 g/dL (transfusion allowed) Hepatic AST and ALT ≤ 5 times normal Bilirubin < 2 times normal Renal Creatinine ≤ 1.5 mg/dL Glomerular filtration rate OR 12-hour creatinine clearance ≥ 60 mL/min/1.73m^2 Cardiovascular Ejection fraction ≥ 55% by echocardiogram or MUGA OR Fractional shortening ≥ 30% OR above lower limit of normal by echocardiogram Pulmonary Normal lung function No dyspnea at rest No exercise intolerance No oxygen requirement Other 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 PRIOR CONCURRENT THERAPY: Biologic therapy At least 2 weeks since prior biologic or other non-myelosuppressive therapy Chemotherapy See Disease Characteristics At least 2 weeks since prior chemotherapy More than 3 months since prior myeloablative therapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 6 months since prior craniospinal, total abdominal, or whole lung radiotherapy 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 Surgery Not specified Other 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

Sites / Locations

  • Children's Hospital Los Angeles
  • UCSF Comprehensive Cancer Center
  • Indiana University Cancer Center
  • Children's Hospital Boston
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
May 14, 2004
Last Updated
October 14, 2010
Sponsor
Children's Hospital Los Angeles
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00083135
Brief Title
N2000-01: Double Infusion of Iodine I 131 Metaiodobenzylguanidine Followed by Autologous Stem Cell Transplantation
Official Title
I-MIBG Escalating Dose Rapid Sequence Double Infusion Followed By Autologous Stem Cell Infusion For Refractory Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
February 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Children's Hospital Los Angeles
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Giving iodine I 131 metaiodobenzylguanidine (^131I-MIBG) may kill neuroblastoma cells by delivering radiation directly to the tumor. A stem cell transplant using the patient's stem cells may be able to replace blood-forming cells destroyed by radiation therapy. PURPOSE: This phase I trial is studying the side effects and best dose of a double infusion of ^131I-MIBG followed by autologous stem cell transplantation in treating patients with refractory neuroblastoma.
Detailed Description
OBJECTIVES: Primary 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. Secondary 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
recurrent neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of neuroblastoma Confirmed by at least 1 of the following methods: Histology Clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites High-risk disease Poor response to induction therapy OR relapse defined by any of the following: 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 immunocytology 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 immunocytology 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 PATIENT CHARACTERISTICS: Age 1 to 30 Performance status ECOG 0-2 Life expectancy Less than 1 year Hematopoietic Absolute neutrophil count ≥ 500/mm^3 Platelet count ≥ 50,000/mm^3 (without transfusion) Hemoglobin ≥ 8 g/dL (transfusion allowed) Hepatic AST and ALT ≤ 5 times normal Bilirubin < 2 times normal Renal Creatinine ≤ 1.5 mg/dL Glomerular filtration rate OR 12-hour creatinine clearance ≥ 60 mL/min/1.73m^2 Cardiovascular Ejection fraction ≥ 55% by echocardiogram or MUGA OR Fractional shortening ≥ 30% OR above lower limit of normal by echocardiogram Pulmonary Normal lung function No dyspnea at rest No exercise intolerance No oxygen requirement Other 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 PRIOR CONCURRENT THERAPY: Biologic therapy At least 2 weeks since prior biologic or other non-myelosuppressive therapy Chemotherapy See Disease Characteristics At least 2 weeks since prior chemotherapy More than 3 months since prior myeloablative therapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 6 months since prior craniospinal, total abdominal, or whole lung radiotherapy 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 Surgery Not specified Other 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine K. Matthay, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gregory Yanik, MD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John M. Maris, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
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
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5289
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
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
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
19171714
Citation
Matthay KK, Quach A, Huberty J, Franc BL, Hawkins RA, Jackson H, Groshen S, Shusterman S, Yanik G, Veatch J, Brophy P, Villablanca JG, Maris JM. Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. J Clin Oncol. 2009 Mar 1;27(7):1020-5. doi: 10.1200/JCO.2007.15.7628. Epub 2009 Jan 26.
Results Reference
result
PubMed Identifier
19805691
Citation
Taggart DR, Han MM, Quach A, Groshen S, Ye W, Villablanca JG, Jackson HA, Mari Aparici C, Carlson D, Maris J, Hawkins R, Matthay KK. Comparison of iodine-123 metaiodobenzylguanidine (MIBG) scan and [18F]fluorodeoxyglucose positron emission tomography to evaluate response after iodine-131 MIBG therapy for relapsed neuroblastoma. J Clin Oncol. 2009 Nov 10;27(32):5343-9. doi: 10.1200/JCO.2008.20.5732. Epub 2009 Oct 5.
Results Reference
result

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N2000-01: Double Infusion of Iodine I 131 Metaiodobenzylguanidine Followed by Autologous Stem Cell Transplantation

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