Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01798004




Registration number
NCT01798004
Ethics application status
Date submitted
6/01/2013
Date registered
25/02/2013
Date last updated
15/07/2024

Titles & IDs
Public title
Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
Scientific title
Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma
Secondary ID [1] 0 0
NCI-2012-02211
Secondary ID [2] 0 0
ANBL12P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ganglioneuroblastoma 0 0
Stage 1 Neuroblastoma 0 0
Stage 2 Neuroblastoma 0 0
Stage 2A Neuroblastoma 0 0
Stage 2B Neuroblastoma 0 0
Stage 3 Neuroblastoma 0 0
Stage 4 Neuroblastoma 0 0
Stage 4S Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Autologous Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Busulfan
Treatment: Drugs - Cisplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Other - External Beam Radiation Therapy
Treatment: Other - Filgrastim
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Melphalan
Treatment: Drugs - Mesna
Treatment: Surgery - Peripheral Blood Stem Cell Transplantation
Other interventions - Pharmacological Study
Treatment: Drugs - Topotecan Hydrochloride
Treatment: Drugs - Vincristine Sulfate

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.


Treatment: Surgery: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant

Treatment: Drugs: Busulfan
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Other: External Beam Radiation Therapy
Undergo EBRT

Treatment: Other: Filgrastim
Given SC or IV

Other interventions: Laboratory Biomarker Analysis
Optional correlative studies

Treatment: Drugs: Melphalan
Given IV

Treatment: Drugs: Mesna
Given IV

Treatment: Surgery: Peripheral Blood Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Topotecan Hydrochloride
Given IV

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Intervention code [4] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Tolerability of BuMel Regimen
Timepoint [1] 0 0
Up to 28 days post-consolidation therapy, up to 1 year

Eligibility
Key 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
Minimum age
No limit
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2024
Sample size
Target
Accrual to date
Final
150
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Colorado
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United States of America
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Connecticut
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United States of America
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Delaware
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United States of America
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District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
Country [20] 0 0
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Missouri
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Nebraska
Country [22] 0 0
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
Country [29] 0 0
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Oklahoma
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Tennessee
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Texas
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Virginia
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Washington
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United States of America
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Wisconsin
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
State/province [39] 0 0
Nova Scotia
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Canada
State/province [40] 0 0
Ontario
Country [41] 0 0
Canada
State/province [41] 0 0
Quebec
Country [42] 0 0
New Zealand
State/province [42] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mary Meaghan P Granger
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01798004