Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01175356
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 99
• Locations: 23
• Arm: 1
• Patients Per Site: 4.3

Study Details

Study Description

Brief Summary

This clinical trial is studying induction therapy followed by meta-iodobenzylguanidine (MIBG) labeled with iodine-131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as MIBG labeled with iodine-131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as cisplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant can replace blood-forming cells that are damaged by MIBG labeled with iodine-131 and chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Disseminated Neuroblastoma; Ganglioneuroblastoma; Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Regional Neuroblastoma; Stage 4S Neuroblastoma	Drug: cyclophosphamide; Drug: topotecan hydrochloride; Drug: cisplatin; Drug: etoposide phosphate; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Radiation: iobenguane I 131; Procedure: therapeutic conventional surgery; Drug: busulfan; Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: 3-dimensional conformal radiation therapy; Radiation: external beam radiation therapy; Radiation: intensity-modulated radiation therapy; Drug: isotretinoin; Other: pharmacological study; Other: questionnaire administration; Other: laboratory biomarker analysis	N/A

Detailed Description

PRIMARY OBJECTIVE:

1. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131]) delivered after multi-agent chemotherapy, and b) post-induction busulfan/melphalan (Bu/Mel) consolidation therapy.

SECONDARY OBJECTIVES:

1. To assess the tolerability of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-induction Bu/Mel consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy.

TERTIARY OBJECTIVES:

1. To assess the response rate after a regimen of induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy.

2. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response.

3. To assess the relative reliability of 123 I-MIBG and fludeoxyglucose F-18 (18FDG)-positron emission tomography (PET) imaging in assessment of tumor activity at diagnosis, and prior to surgical resection.

4. To compare detectable tumor burden on the pre-surgical resection radioiodinated-MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan.

5. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG.

6. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and relate exposure to SOS incidence.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.

Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2.

Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5.

Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3.

Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive iobenguane I 131 IV over 90-120 minutes on day 1.

SURGERY: Patients undergo surgery after course 4 or before consolidation therapy.

CONSOLIDATION THERAPY: Within 10-12 weeks from the date of iobenguane I 131 infusion, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1.

AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0.

RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2 dimensional [D], 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease.

MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG Followed by Myeloablative Busulfan/Melphalan (Bu/Mel) for Newly Diagnosed High-Risk Neuroblastoma
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Sep 28, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (131I-MIBG, chemotherapy) See Detailed Description.

Drug: cyclophosphamide; Given IV; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: topotecan hydrochloride; Given IV; Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO ; Drug: cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP ; Drug: etoposide phosphate; Given IV; Other Names: ETOP Etopophos ; Drug: vincristine sulfate; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria ; Radiation: iobenguane I 131; Given IV; Other Names: 131 I-MIBG I 131 Metaiodobenzylguanidine Iodine I 131 Metaiodobenzylguanidine ; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: busulfan; Given IV; Other Names: BSF BU Misulfan Mitosan Myeloleukon ; Drug: melphalan; Given IV; Other Names: Alkeran CB-3025 L-PAM L-phenylalanine mustard L-Sarcolysin ; Procedure: autologous hematopoietic stem cell transplantation; Undergo autologous in vitro-treated peripheral blood stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Undergo autologous in vitro-treated peripheral blood stem cell transplantation; Other Names: in vitro-treated PBPC transplantation in vitro-treated PBSC in vitro-treated peripheral blood progenitor cell transplantation PBPC transplantation, in vitro-treated peripheral blood progenitor cell transplantation, in vitro-treated ; Radiation: 3-dimensional conformal radiation therapy; Undergo radiotherapy; Other Names: 3D conformal radiation therapy 3D-CRT ; Radiation: external beam radiation therapy; Undergo radiotherapy; Other Names: EBRT ; Radiation: intensity-modulated radiation therapy; Undergo radiotherapy; Other Names: IMRT ; Drug: isotretinoin; Given PO; Other Names: 13-CRA Amnesteem Cistane Claravis Sotret ; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies ; Other: questionnaire administration; Ancillary studies; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131 [Up to 6 weeks after course 5 of induction]

   Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%.

2. Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy [Up to day -6 of conditioning]

   Number of MIBG avid patients who receive 131I-MIBG and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint x 100%.

Secondary Outcome Measures

1. Incidence of Unacceptable Toxicity and Sinusoidal Obstruction Syndrome (SOS), Assessed by Common Terminology Criteria (CTV)v.4.0 for Toxicity Assessment and Grading for I-MIBG [Up to 6 weeks after course 5 of induction]

   Number of patients who had an unacceptable toxicity or experienced SOS. Unacceptable toxicity was defined as CTC Grade 4-5 Pulmonary/Respiratory.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:

• Patients with newly diagnosed neuroblastoma with International Neuroblastoma

Staging System (INSS) stage 4 are eligible with the following:

• v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of additional biologic features

• Age > 18 months (> 547 days) regardless of biologic features

• Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown

• Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:

• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features

• Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status

• Patients with newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features

• Patients >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S

• Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per low- or intermediate-risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age and/or gender as follows:

• 0.6 mg/dL (1 to < 2 years of age)

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) ( >= 16 years of age)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age

• Shortening fraction >= 27% by echocardiogram or

• Ejection fraction >= 50% by radionuclide evaluation

• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method

• Female patients who are lactating must agree to stop breast-feeding

• Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible

• Patients are not eligible if they have received local radiation which includes any of the following: 1200 centigray (cGy) to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
5	University of California San Francisco Medical Center-Parnassus	San Francisco	California	United States	94143
6	Children's Hospital Colorado	Aurora	Colorado	United States	80045
7	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
8	Children's National Medical Center	Washington	District of Columbia	United States	20010
9	University of Chicago	Chicago	Illinois	United States	60637
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
11	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
12	University of North Carolina	Chapel Hill	North Carolina	United States	27599
13	Duke University Medical Center	Durham	North Carolina	United States	27710
14	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
15	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
18	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
19	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
20	Seattle Children's Hospital	Seattle	Washington	United States	98105
21	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
22	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
23	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brian Weiss, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT01175356
• Other Study ID Numbers: ANBL09P1; NCI-2011-01745; CDR0000682629; ANBL09P1; ANBL09P1; U10CA180886; U10CA098543
• First Posted: Aug 4, 2010
• Last Update Posted: Mar 7, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Neuroblastoma; Ganglioneuroblastoma; Cyclophosphamide; Melphalan; Busulfan; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Topotecan; Etoposide phosphate; 3-Iodobenzylguanidine; Isotretinoin

Study Results

Participant Flow

Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
Period Title: Overall Study
STARTED	99
COMPLETED	18
NOT COMPLETED	81

Baseline Characteristics

Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
Overall Participants	99
Age (Count of Participants)
<=18 years	99 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.2 (2.9)
Sex: Female, Male (Count of Participants)
Female	39 39.4%
Male	60 60.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 6.1%
Not Hispanic or Latino	86 86.9%
Unknown or Not Reported	7 7.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%
Asian	3 3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	18 18.2%
White	64 64.6%
More than one race	0 0%
Unknown or Not Reported	13 13.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131
Description	Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%.
Time Frame	Up to 6 weeks after course 5 of induction

Outcome Measure Data

Analysis Population Description

Includes patients who met criteria to receive 131I-MIBG but went off protocol therapy before receiving a dose assignment, but excludes patients that could not continue onto 131I-MIBG therapy due to lack of an open treatment slot. The definition of receiving MIBG labeled with iodine-131 is receiving 131I-MIBG.

Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
Measure Participants	68
Number (95% Confidence Interval) [Percentage of participants]	86.8 87.7%

2. Primary Outcome

Title	Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy
Description	Number of MIBG avid patients who receive 131I-MIBG and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint x 100%.
Time Frame	Up to day -6 of conditioning

Outcome Measure Data

Analysis Population Description

Includes patients who met criteria to receive 131I-MIBG but went off protocol therapy before receiving a dose assignment, but excludes patients that could not receive 131I-MIBG therapy due to lack of an open treatment slot. The definition of receiving Bu/Mel conditioning is receiving the first dose of planned Busulfan on Day -6 of conditioning.

Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
Measure Participants	45
Number (95% Confidence Interval) [Percentage of participants]	82.2 83%

3. Secondary Outcome

Title	Incidence of Unacceptable Toxicity and Sinusoidal Obstruction Syndrome (SOS), Assessed by Common Terminology Criteria (CTV)v.4.0 for Toxicity Assessment and Grading for I-MIBG
Description	Number of patients who had an unacceptable toxicity or experienced SOS. Unacceptable toxicity was defined as CTC Grade 4-5 Pulmonary/Respiratory.
Time Frame	Up to 6 weeks after course 5 of induction

Outcome Measure Data

Analysis Population Description

Includes patients who received 131I-MIBG therapy.

Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
Measure Participants	53
Count of Participants [Participants]	3 3%

Adverse Events

Adverse Event Reporting Description	The Total Number of Participants at Risk (n=98) in the Adverse Events tables does not match the number of patients in the Participant Flow (n=99) because ineligible patients were excluded (n=1).
Arm/Group Title	Treatment (131I-MIBG, Chemotherapy)
Arm/Group Description	Induction with multi-agent chemotherapy and MIBG labeled with iodine-131/isotretinoin/vincristine followed by Consolidation with BuMel Chemotherapy+ASCT+XRT.
All Cause Mortality
	Treatment (131I-MIBG, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (131I-MIBG, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	27/98 (27.6%)
Cardiac disorders
39000-Heart failure	1/98 (1%)	1
74500-Sinus tachycardia	1/98 (1%)	1
Gastrointestinal disorders
10300-Abdominal pain	1/98 (1%)	1
14900-Ascites	6/98 (6.1%)	6
55600-Mucositis oral	2/98 (2%)	2
General disorders
24600-Death NOS	13/98 (13.3%)	13
37200-General disorders and administration site conditions - Other specify	1/98 (1%)	1
55700-Multi-organ failure	2/98 (2%)	2
60600-Pain	1/98 (1%)	1
Hepatobiliary disorders
21600-Cholecystitis	1/98 (1%)	1
40000-Hepatic failure	2/98 (2%)	2
40400-Hepatic pain	2/98 (2%)	2
40600-Hepatobiliary disorders - Other specify	2/98 (2%)	2
66500-Portal hypertension	3/98 (3.1%)	3
Infections and infestations
44800-Infections and infestations - Other specify	2/98 (2%)	2
53100-Lung infection	1/98 (1%)	1
73700-Sepsis	3/98 (3.1%)	3
Investigations
10900-Activated partial thromboplastin time prolonged	2/98 (2%)	2
11600-Alanine aminotransferase increased	4/98 (4.1%)	4
15000-Aspartate aminotransferase increased	4/98 (4.1%)	4
17400-Blood bilirubin increased	8/98 (8.2%)	8
45800-INR increased	2/98 (2%)	2
88200-Weight gain	5/98 (5.1%)	5
88300-Weight loss	2/98 (2%)	2
Metabolism and nutrition disorders
10700-Acidosis	1/98 (1%)	1
13500-Anorexia	1/98 (1%)	1
41600-Hyperkalemia	1/98 (1%)	1
41800-Hypernatremia	1/98 (1%)	1
42600-Hypoalbuminemia	2/98 (2%)	2
43100-Hypokalemia	2/98 (2%)	3
43300-Hyponatremia	3/98 (3.1%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
58000-Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify	1/98 (1%)	1
Nervous system disorders
72500-Reversible posterior leukoencephalopathy syndrome	1/98 (1%)	1
Respiratory, thoracic and mediastinal disorders
43900-Hypoxia	5/98 (5.1%)	5
65900-Pleural effusion	3/98 (3.1%)	3
69000-Pulmonary hypertension	1/98 (1%)	1
71600-Respiratory thoracic and mediastinal disorders - Other specify	1/98 (1%)	1
Vascular disorders
43600-Hypotension	1/98 (1%)	1
Other (Not Including Serious) Adverse Events
	Treatment (131I-MIBG, Chemotherapy)
	Affected / at Risk (%)	# Events
Total	86/98 (87.8%)
Blood and lymphatic system disorders
13200-Anemia	24/98 (24.5%)	49
33300-Febrile neutropenia	54/98 (55.1%)	81
Cardiac disorders
20000-Cardiac arrest	1/98 (1%)	1
78900-Supraventricular tachycardia	1/98 (1%)	1
Ear and labyrinth disorders
38900-Hearing impaired	9/98 (9.2%)	11
Gastrointestinal disorders
10100-Abdominal distension	1/98 (1%)	1
10300-Abdominal pain	7/98 (7.1%)	7
14900-Ascites	5/98 (5.1%)	5
22100-Colitis	1/98 (1%)	1
25700-Diarrhea	6/98 (6.1%)	7
29400-Enterocolitis	1/98 (1%)	1
36400-Gastritis	1/98 (1%)	1
44600-Ileus	1/98 (1%)	1
55600-Mucositis oral	19/98 (19.4%)	22
57600-Nausea	15/98 (15.3%)	17
59700-Oral pain	2/98 (2%)	2
81900-Typhlitis	1/98 (1%)	1
87900-Vomiting	18/98 (18.4%)	20
General disorders
33900-Fever	1/98 (1%)	1
37200-General disorders and administration site conditions - Other specify	1/98 (1%)	1
60600-Pain	7/98 (7.1%)	8
Immune system disorders
12000-Allergic reaction	1/98 (1%)	1
13100-Anaphylaxis	1/98 (1%)	1
Infections and infestations
20500-Catheter related infection	10/98 (10.2%)	11
25600-Device related infection	1/98 (1%)	1
44800-Infections and infestations - Other specify	17/98 (17.3%)	18
53100-Lung infection	2/98 (2%)	2
61100-Pancreas infection	1/98 (1%)	1
73700-Sepsis	4/98 (4.1%)	4
74600-Sinusitis	1/98 (1%)	1
75200-Skin infection	1/98 (1%)	1
76000-Small intestine infection	1/98 (1%)	1
82300-Upper respiratory infection	1/98 (1%)	1
83100-Urinary tract infection	4/98 (4.1%)	4
88900-Wound infection	2/98 (2%)	2
Injury, poisoning and procedural complications
13800-Aortic injury	1/98 (1%)	1
45700-Injury poisoning and procedural complications - Other specify	1/98 (1%)	1
47300-Intraoperative hepatobiliary injury	1/98 (1%)	1
47700-Intraoperative renal injury	1/98 (1%)	1
Investigations
10900-Activated partial thromboplastin time prolonged	1/98 (1%)	1
11600-Alanine aminotransferase increased	14/98 (14.3%)	15
15000-Aspartate aminotransferase increased	14/98 (14.3%)	14
17400-Blood bilirubin increased	1/98 (1%)	1
24100-Creatinine increased	2/98 (2%)	2
34000-Fibrinogen decreased	1/98 (1%)	1
37500-GGT increased	1/98 (1%)	1
52600-Lipase increased	1/98 (1%)	1
53700-Lymphocyte count decreased	21/98 (21.4%)	49
58300-Neutrophil count decreased	27/98 (27.6%)	56
65800-Platelet count decreased	28/98 (28.6%)	59
88200-Weight gain	1/98 (1%)	1
88300-Weight loss	1/98 (1%)	1
88500-White blood cell decreased	23/98 (23.5%)	50
Metabolism and nutrition disorders
10700-Acidosis	1/98 (1%)	1
13500-Anorexia	33/98 (33.7%)	48
24700-Dehydration	12/98 (12.2%)	12
41300-Hypercalcemia	1/98 (1%)	1
41400-Hyperglycemia	9/98 (9.2%)	12
41600-Hyperkalemia	2/98 (2%)	2
41700-Hypermagnesemia	1/98 (1%)	1
41800-Hypernatremia	1/98 (1%)	1
42600-Hypoalbuminemia	3/98 (3.1%)	3
42700-Hypocalcemia	3/98 (3.1%)	3
42900-Hypoglycemia	1/98 (1%)	1
43100-Hypokalemia	33/98 (33.7%)	36
43200-Hypomagnesemia	2/98 (2%)	2
43300-Hyponatremia	8/98 (8.2%)	9
43500-Hypophosphatemia	16/98 (16.3%)	18
54900-Metabolism and nutrition disorders - Other specify	2/98 (2%)	2
Musculoskeletal and connective tissue disorders
18200-Bone pain	1/98 (1%)	1
37300-Generalized muscle weakness	1/98 (1%)	1
60700-Pain in extremity	2/98 (2%)	2
Nervous system disorders
10500-Abducens nerve disorder	1/98 (1%)	1
38800-Headache	2/98 (2%)	2
79100-Syncope	1/98 (1%)	1
Psychiatric disorders
11400-Agitation	2/98 (2%)	2
13700-Anxiety	1/98 (1%)	1
25400-Depression	1/98 (1%)	1
Renal and urinary disorders
11100-Acute kidney injury	1/98 (1%)	1
39300-Hematuria	2/98 (2%)	2
71100-Renal calculi	1/98 (1%)	1
Respiratory, thoracic and mediastinal disorders
19300-Bronchospasm	1/98 (1%)	1
29700-Epistaxis	3/98 (3.1%)	4
43900-Hypoxia	8/98 (8.2%)	8
64900-Pharyngeal mucositis	1/98 (1%)	1
66400-Pneumothorax	1/98 (1%)	1
68700-Pulmonary edema	2/98 (2%)	2
69000-Pulmonary hypertension	1/98 (1%)	1
71500-Respiratory failure	2/98 (2%)	2
78100-Stridor	1/98 (1%)	2
Skin and subcutaneous tissue disorders
74700-Skin and subcutaneous tissue disorders - Other specify	1/98 (1%)	1
Surgical and medical procedures
79000-Surgical and medical procedures - Other specify	1/98 (1%)	1
Vascular disorders
39100-Hematoma	1/98 (1%)	1
42100-Hypertension	1/98 (1%)	2
43600-Hypotension	4/98 (4.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior approval.