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CompletedNCT01798004Updated Jul 15, 2024Results posted

Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma

A Phase 1 interventional study of Autologous Hematopoietic Stem Cell Transplantation and Busulfan in Ganglioneuroblastoma, Stage 1 Neuroblastoma and Stage 2 Neuroblastoma, sponsored by Children's Oncology Group. Completed at 123 sites in 4 countries. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2024-07-15.

Sponsored by Children's Oncology Group · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
150
Allocation
Not applicable
Ages
Up to 30 Years
Sex
All
01

Study summary

This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine if the acute toxicity of an autologous stem cell transplant with a busulfan-melphalan (BuMel) based regimen is tolerable when given as consolidation therapy for high-risk neuroblastoma.

EXPLORATORY OBJECTIVES:

I. To determine the incidence of non-hematologic organ toxicity (grade 3 and higher) and all cause mortality in patients undergoing autologous stem cell transplant with a BuMel based regimen followed by local radiotherapy for the treatment of high-risk neuroblastoma.

II. To describe response rates, event-free survival (EFS), and overall survival (OS) for patients undergoing induction therapy followed by consolidation with myeloablative BuMel preparative regimen and local radiotherapy for the treatment of high-risk neuroblastoma.

III. To correlate busulfan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival.

IV. To determine the feasibility of performing Curie scores in "real time," as assessed by central scan committee review of a 123 I-meta-iodobenzylguanidine (MIBG) scan obtained after cycle 4 of induction therapy.

V. To examine the concordance between central reviewers and institutional reviewers in performing Curie scoring at diagnosis and after cycle 4 of induction therapy.

VI. To determine the feasibility of detecting aberrations in the anaplastic lymphoma kinase (ALK) gene in tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma.

VII. To determine the feasibility of performing molecular profiling of neuroblastoma tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma.

VIII. To correlate melphalan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival.

OUTLINE:

INDUCTION THERAPY:

COURSES 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes, topotecan hydrochloride IV over 30 minutes on days 1-5 and filgrastim subcutaneously (SC) or IV once daily (QD) beginning on day 6. Treatment repeats every 3 weeks for 2 courses.

COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.

COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, doxorubicin hydrochloride IV over 24 hours on days 1-3 and mesna IV over 15-30 minutes on days 1-2. Treatment repeats every 3 weeks for 1 course.

Treatment continues in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo autologous stem cell transplant (ASCT) on day 0 and filgrastim SC or IV beginning on day 0.

Some patients also undergo external beam radiation therapy (EBRT) after induction and consolidation.

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

02

Conditions studied

  • Ganglioneuroblastoma
  • Stage 1 Neuroblastoma
  • Stage 2 Neuroblastoma
  • Stage 2A Neuroblastoma
  • Stage 2B Neuroblastoma
  • Stage 3 Neuroblastoma
  • Stage 4 Neuroblastoma
  • Stage 4S Neuroblastoma
03

In context

Neuroblastoma

625 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.

This study's enrollment of 150 is above the median of 32 across 475 interventional studies indexed under Neuroblastoma.

Browse Neuroblastoma studies →

Lead sponsor

Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 30 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients must have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) 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 avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
    • Age > 18 months (> 547 days) regardless of biologic features or
    • 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 indeterminate/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), regardless of age or additional biologic features or
    • Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
  • Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
  • Patients with newly diagnosed neuroblastoma with INSS stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features
  • Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S
  • Patients must not have had 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 a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology

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

    • Age 1 month to \< 6 months: 0.4 mg/dL
    • Age 6 months to \< 1 year: 0.5 mg/dL
    • Age 1 to \< 2 years: 0.6 mg/dL
    • Age 2 to \< 6 years: 0.8 mg/dL
    • Age 6 to \< 10 years: 1 mg/dL
    • Age 10 to \< 13 years: 1.2 mg/dL
    • Age 13 to \< 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females)
    • Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females)
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) \< 10 x ULN for age
  • Shortening fraction of >= 27% by echocardiogram, or
  • Ejection fraction of >= 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 that determined to be feasible at the collecting institution, 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

Exclusion Criteria:

  • Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
150 participants (actual)

Study arms

  • Experimental
    Treatment (induction therapy, consolidation therapy, ASCT)

    INDUCTION THERAPY: COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses. COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses. COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course. Treatment continues in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0. Some patients also undergo EBRT after induction and consolidation.

    Procedure: Autologous Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cisplatin · Drug: Cyclophosphamide · Drug: Doxorubicin Hydrochloride · Drug: Etoposide · Radiation: External Beam Radiation Therapy · Biological: Filgrastim · Other: Laboratory Biomarker Analysis · Drug: Melphalan · Drug: Mesna · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Drug: Topotecan Hydrochloride · Drug: Vincristine Sulfate

Interventions

  • ProcedureAutologous Hematopoietic Stem Cell Transplantation

    Undergo autologous peripheral blood stem cell transplant

    Also known as: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous

  • DrugBusulfan

    Given IV

    Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

  • DrugCisplatin

    Given IV

    Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

  • DrugDoxorubicin Hydrochloride

    Given IV

    Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

  • DrugEtoposide

    Given IV

    Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

  • RadiationExternal Beam Radiation Therapy

    Undergo EBRT

    Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

  • BiologicalFilgrastim

    Given SC or IV

    Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio

  • OtherLaboratory Biomarker Analysis

    Optional correlative studies

  • DrugMelphalan

    Given IV

    Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

  • DrugMesna

    Given IV

    Also known as: 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna, Mercaptoethane Sulfonate, Mercaptoethanesulfonate, Mesnex, Mesnil, Mesnum, Mexan, Mistabron, Mistabronco, Mitexan, Mucofluid, Mucolene, UCB 3983, Uromitexan, Ziken

  • ProcedurePeripheral Blood Stem Cell Transplantation

    Undergo autologous peripheral blood stem cell transplant

    Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

  • OtherPharmacological Study

    Correlative studies

  • DrugTopotecan Hydrochloride

    Given IV

    Also known as: Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride, Potactasol, SKF S 104864 A, SKF S-104864-A, SKF S104864A, Topotec, Topotecan HCl, topotecan hydrochloride (oral)

  • DrugVincristine Sulfate

    Given IV

    Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

06

What researchers measure

Primary outcomes

  1. The Tolerability of BuMel Regimen

    Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome \[SOS\] or Grade 4-5 pulmonary toxicity per Common Toxicity Criteria \[CTC\] v.4.0) during the Consolidation phase of therapy.

    Time frame: Up to 28 days post-consolidation therapy, up to 1 year

Other outcomes

  1. Incidence of Non-hematologic Organ Toxicity (Grade 3 and Higher) and All Cause Mortality Graded According to CTC v4.0

    Assessed by a descriptive analysis of the incidence of grade 3-5 non-hematologic toxicities (CTC v4.0) and all-cause mortality during consolidation therapy. In addition, a descriptive analysis of "late" onset grade 4-5 pulmonary and hepatic complications that occur within 180 days of the start of consolidation therapy will be examined, regardless if the patient has proceeded to other therapy (including chimeric antibody) during that 180 day period.

    Time frame: Up to 180 days

  2. Response Rate Determined Using the International Response Criteria

    Time frame: Up to 5 years

  3. EFS

    Time frame: Up to 5 years

  4. Overall Survival

    Time frame: Up to 5 years

  5. First Dose Area Under the Curve (AUC) and Average Daily AUC for Busulfan

    Relationship with occurrence of non-hematologic toxicities assessed by a descriptive analysis. Association between busulfan exposure levels as measured by the area under the curve (AUC) and event-free survival and overall survival will be examined using Cox proportional hazards models.

    Time frame: Within 28 days following consolidation

  6. Percentage of Centrally Reviewed Post-course 4 MIBG Scans Reporting a Curie Score Considered to Have Been Determined in "Real Time"

    Time frame: Up to week 12 (course 4 of induction therapy)

  7. Percentage of MIBG Scans Receiving Institutionally and Centrally Reviewed and Automated Advanced Assisted Scoring Platform Curie Scores Within 1 Unit of Each Other

    Cohen's kappa will be calculated to evaluate the concordance in Curie scores between each of the scoring methods at each time point. Up to 160 MIBG scans are expected at diagnosis and up to 144 MIBG scans from the 90% of patients estimated to be MIBG avid are projected post-course 4 of induction therapy, for a total of up to 304 MIBG scans.

    Time frame: Up to week 12 (course 4 of induction therapy)

  8. Proportion of High-risk Neuroblastoma Patients for Whom ALK Status Can be Obtained

    Time frame: Within 6 weeks of diagnosis

  9. Proportion of High-risk Neuroblastoma Patients With MYCN Non-amplified Tumors for Whom Molecular Profiling Results Can be Obtained

    Time frame: Within 8 weeks of diagnosis

  10. Melphalan Pharmacokinetics and the Combination of Busulfan and Melphalan AUC (Optional)

    A descriptive analysis of the relationship between melphalan pharmacokinetics and the combination of busulfan and melphalan AUC with the occurrence of non-hematologic toxicities within 28 days following completion of consolidation will be assessed. In addition, the association between melphalan exposure levels as measured by the AUC and event-free survival and overall survival will be examined using Cox proportional hazards models.

    Time frame: Within 28 days post-consolidation

07

Results

Posted Feb 9, 2017

Participant flow

Participant flow — Overall Study
MilestoneAll Patients
Started150
Completed63
Not completed87
Withdrew: Death2
Withdrew: Lack of efficacy8
Withdrew: Physician decision25
Withdrew: Withdrawal by subject4
Withdrew: Ineligible4
Withdrew: Patient/parent refusal7
Withdrew: Initiation of other non-protocol therapy5
Withdrew: Enrollment another cog therapeutic trial32

Outcome measures

PrimaryThe Tolerability of BuMel Regimen

Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome \[SOS\] or Grade 4-5 pulmonary toxicity per Common Toxicity Criteria \[CTC\] v.4.0) during the Consolidation phase of therapy.

Time frame:
Up to 28 days post-consolidation therapy, up to 1 year
Reported as:
Number · participants
The Tolerability of BuMel Regimen
participantsAll Patients
The Tolerability of BuMel Regimen9
Other pre-specifiedIncidence of Non-hematologic Organ Toxicity (Grade 3 and Higher) and All Cause Mortality Graded According to CTC v4.0

Assessed by a descriptive analysis of the incidence of grade 3-5 non-hematologic toxicities (CTC v4.0) and all-cause mortality during consolidation therapy. In addition, a descriptive analysis of "late" onset grade 4-5 pulmonary and hepatic complications that occur within 180 days of the start of consolidation therapy will be examined, regardless if the patient has proceeded to other therapy (including chimeric antibody) during that 180 day period.

Time frame:
Up to 180 days

Results for this outcome have not been posted.

Other pre-specifiedResponse Rate Determined Using the International Response Criteria
Time frame:
Up to 5 years

Results for this outcome have not been posted.

Other pre-specifiedEFS
Time frame:
Up to 5 years

Results for this outcome have not been posted.

Other pre-specifiedOverall Survival
Time frame:
Up to 5 years

Results for this outcome have not been posted.

Other pre-specifiedFirst Dose Area Under the Curve (AUC) and Average Daily AUC for Busulfan

Relationship with occurrence of non-hematologic toxicities assessed by a descriptive analysis. Association between busulfan exposure levels as measured by the area under the curve (AUC) and event-free survival and overall survival will be examined using Cox proportional hazards models.

Time frame:
Within 28 days following consolidation

Results for this outcome have not been posted.

Other pre-specifiedPercentage of Centrally Reviewed Post-course 4 MIBG Scans Reporting a Curie Score Considered to Have Been Determined in "Real Time"
Time frame:
Up to week 12 (course 4 of induction therapy)

Results for this outcome have not been posted.

Other pre-specifiedPercentage of MIBG Scans Receiving Institutionally and Centrally Reviewed and Automated Advanced Assisted Scoring Platform Curie Scores Within 1 Unit of Each Other

Cohen's kappa will be calculated to evaluate the concordance in Curie scores between each of the scoring methods at each time point. Up to 160 MIBG scans are expected at diagnosis and up to 144 MIBG scans from the 90% of patients estimated to be MIBG avid are projected post-course 4 of induction therapy, for a total of up to 304 MIBG scans.

Time frame:
Up to week 12 (course 4 of induction therapy)

Results for this outcome have not been posted.

Other pre-specifiedProportion of High-risk Neuroblastoma Patients for Whom ALK Status Can be Obtained
Time frame:
Within 6 weeks of diagnosis

Results for this outcome have not been posted.

Other pre-specifiedProportion of High-risk Neuroblastoma Patients With MYCN Non-amplified Tumors for Whom Molecular Profiling Results Can be Obtained
Time frame:
Within 8 weeks of diagnosis

Results for this outcome have not been posted.

Other pre-specifiedMelphalan Pharmacokinetics and the Combination of Busulfan and Melphalan AUC (Optional)

A descriptive analysis of the relationship between melphalan pharmacokinetics and the combination of busulfan and melphalan AUC with the occurrence of non-hematologic toxicities within 28 days following completion of consolidation will be assessed. In addition, the association between melphalan exposure levels as measured by the AUC and event-free survival and overall survival will be examined using Cox proportional hazards models.

Time frame:
Within 28 days post-consolidation

Results for this outcome have not been posted.

Adverse events

Collected over Four ineligible patients were excluded from the Adverse Event tables, so even though 150 patients enrolled on the study and are summarized in the Participant Flow template, only 146 were at risk for adverse events.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
All Patients—10/146 (6.8%)82/146 (56.2%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventAll Patients
Death NOSGeneral disorders2/146
Lung infectionInfections and infestations2/146
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/146
DyspneaRespiratory, thoracic and mediastinal disorders2/146
HypoxiaRespiratory, thoracic and mediastinal disorders2/146
Respiratory failureRespiratory, thoracic and mediastinal disorders2/146
AscitesGastrointestinal disorders1/146
Multi-organ failureGeneral disorders1/146
Hepatobiliary disorders - Other, specifyHepatobiliary disorders1/146
SepsisInfections and infestations1/146
Most frequent other events
Showing 10 of 78
Most frequent other events
EventAll Patients
Mucositis oralGastrointestinal disorders46/146
Febrile neutropeniaBlood and lymphatic system disorders30/146
AnorexiaMetabolism and nutrition disorders28/146
HypokalemiaMetabolism and nutrition disorders27/146
Blood bilirubin increasedInvestigations13/146
Infections and infestations - Other, specifyInfections and infestations11/146
Aspartate aminotransferase increasedInvestigations9/146
NauseaGastrointestinal disorders8/146
HyperglycemiaMetabolism and nutrition disorders8/146
VomitingGastrointestinal disorders7/146

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Patients
<=18 years149
Between 18 and 65 years1
>=65 years0
Age, Continuous
Age, Continuous(Years)All Patients
Median3.1 (0.4 to 18.4)
Sex: Female, Male
Sex: Female, Male(Participants)All Patients
Female60
Male90
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Patients
Hispanic or Latino19
Not Hispanic or Latino129
Unknown or Not Reported2
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Patients
American Indian or Alaska Native0
Asian11
Native Hawaiian or Other Pacific Islander0
Black or African American21
White107
More than one race0
Unknown or Not Reported11
Region of Enrollment
Region of Enrollment(participants)All Patients
New Zealand1
Canada14
United States132
Australia3
08

Study locations

123 sites
  • Children's Hospital of Alabama
    Birmingham, Alabama 35233, United States
  • Kaiser Permanente Downey Medical Center
    Downey, California 90242, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • UCSF Benioff Children's Hospital Oakland
    Oakland, California 94609, United States
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
  • Children's Hospital of Orange County
    Orange, California 92868, United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California 94304, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Rady Children's Hospital - San Diego
    San Diego, California 92123, United States
  • UCSF Medical Center-Parnassus
    San Francisco, California 94143, United States
  • UCSF Medical Center-Mission Bay
    San Francisco, California 94158, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Connecticut Children's Medical Center
    Hartford, Connecticut 06106, United States
  • Alfred I duPont Hospital for Children
    Wilmington, Delaware 19803, United States
  • MedStar Georgetown University Hospital
    Washington, District of Columbia 20007, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010, United States
  • Lee Memorial Health System
    Fort Myers, Florida 33901, United States
  • Golisano Children's Hospital of Southwest Florida
    Fort Myers, Florida 33908, United States
  • University of Florida Health Science Center - Gainesville
    Gainesville, Florida 32610, United States
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida 33021, United States
  • Nemours Children's Clinic-Jacksonville
    Jacksonville, Florida 32207, United States
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
  • Miami Cancer Institute
    Miami, Florida 33176, United States
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • Nemours Children's Hospital
    Orlando, Florida 32827, United States
  • Nemours Children's Clinic - Pensacola
    Pensacola, Florida 32504, United States
  • Johns Hopkins All Children's Hospital
    Saint Petersburg, Florida 33701, United States
  • Saint Joseph's Hospital/Children's Hospital-Tampa
    Tampa, Florida 33607, United States
  • Children's Healthcare of Atlanta - Egleston
    Atlanta, Georgia 30322, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Memorial Health University Medical Center
    Savannah, Georgia 31404, United States
  • Lurie Children's Hospital-Chicago
    Chicago, Illinois 60611, United States
  • University of Illinois
    Chicago, Illinois 60612, United States
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • Saint Jude Midwest Affiliate
    Peoria, Illinois 61637, United States
  • Southern Illinois University School of Medicine
    Springfield, Illinois 62702, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • Ascension Saint Vincent Indianapolis Hospital
    Indianapolis, Indiana 46260, United States
  • Blank Children's Hospital
    Des Moines, Iowa 50309, United States
  • University of Kentucky/Markey Cancer Center
    Lexington, Kentucky 40536, United States
  • Norton Children's Hospital
    Louisville, Kentucky 40202, United States
  • Children's Hospital New Orleans
    New Orleans, Louisiana 70118, United States
  • Maine Children's Cancer Program
    Scarborough, Maine 04074, United States
  • Sinai Hospital of Baltimore
    Baltimore, Maryland 21215, United States
  • Johns Hopkins University/Sidney Kimmel Cancer Center
    Baltimore, Maryland 21287, United States
  • Walter Reed National Military Medical Center
    Bethesda, Maryland 20889-5600, United States
  • Tufts Children's Hospital
    Boston, Massachusetts 02111, United States
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts 02114, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • C S Mott Children's Hospital
    Ann Arbor, Michigan 48109, United States
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
  • Bronson Methodist Hospital
    Kalamazoo, Michigan 49007, United States
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
    Minneapolis, Minnesota 55404, United States
  • University of Minnesota/Masonic Cancer Center
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
  • University of Mississippi Medical Center
    Jackson, Mississippi 39216, United States
  • Columbia Regional
    Columbia, Missouri 65201, United States
  • Children's Mercy Hospitals and Clinics
    Kansas City, Missouri 64108, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Mercy Hospital Saint Louis
    Saint Louis, Missouri 63141, United States
  • Children's Hospital and Medical Center of Omaha
    Omaha, Nebraska 68114, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    Las Vegas, Nevada 89135, United States
  • Summerlin Hospital Medical Center
    Las Vegas, Nevada 89144, United States
  • Nevada Cancer Research Foundation NCORP
    Las Vegas, Nevada 89169, United States
  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    Lebanon, New Hampshire 03756, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Saint Barnabas Medical Center
    Livingston, New Jersey 07039, United States
  • Morristown Medical Center
    Morristown, New Jersey 07960, United States
  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    New Brunswick, New Jersey 08903, United States
  • Newark Beth Israel Medical Center
    Newark, New Jersey 07112, United States
  • Saint Joseph's Regional Medical Center
    Paterson, New Jersey 07503, United States
  • University of New Mexico Cancer Center
    Albuquerque, New Mexico 87106, United States
  • Montefiore Medical Center - Moses Campus
    Bronx, New York 10467, United States
  • NYU Langone Hospital - Long Island
    Mineola, New York 11501, United States
  • The Steven and Alexandra Cohen Children's Medical Center of New York
    New Hyde Park, New York 11040, United States
  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    New York, New York 10032, United States
  • University of Rochester
    Rochester, New York 14642, United States
  • State University of New York Upstate Medical University
    Syracuse, New York 13210, United States
  • Mission Hospital
    Asheville, North Carolina 28801, United States
  • UNC Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina 27599, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
  • Rainbow Babies and Childrens Hospital
    Cleveland, Ohio 44106, United States
  • Cleveland Clinic Foundation
    Cleveland, Ohio 44195, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • Dayton Children's Hospital
    Dayton, Ohio 45404, United States
  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    Toledo, Ohio 43606, United States
  • Mercy Children's Hospital
    Toledo, Ohio 43608, United States
  • University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • Lehigh Valley Hospital - Muhlenberg
    Bethlehem, Pennsylvania 18017, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Prisma Health Richland Hospital
    Columbia, South Carolina 29203, United States
  • BI-LO Charities Children's Cancer Center
    Greenville, South Carolina 29605, United States
  • T C Thompson Children's Hospital
    Chattanooga, Tennessee 37403, United States

Showing the first 100 of 123 sites across 4 countries.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 15, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01798004
Lead sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Feb 25, 2013
Start date
Apr 9, 2013
Primary completion
Jul 28, 2015
Completion
Jun 30, 2024
Results posted
Feb 9, 2017
Last update
Jul 15, 2024

Study contacts

Mary Meaghan P Granger
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.

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