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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00567567




Registration number
NCT00567567
Ethics application status
Date submitted
4/12/2007
Date registered
5/12/2007
Date last updated
1/05/2019

Titles & IDs
Public title
Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
Scientific title
Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma
Secondary ID [1] 0 0
NCI-2009-01065
Secondary ID [2] 0 0
ANBL0532
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Localized Resectable Neuroblastoma 0 0
Localized Unresectable Neuroblastoma 0 0
Recurrent Neuroblastoma 0 0
Regional 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

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

Active Comparator: Consolidation Arm A: single myeloablative consolidation - Patients receive melphalan IV over 15-30 minutes on days -7 to -5, etoposide IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Patients undergo autologous PBSCT on day 0.

Experimental: Consolidation Arm B: tandem myeloablative consolidation - Patients receive thiotepa IV over 2 hours on days -7 to -5, cyclophosphamide IV over 1 hour on days -5 to -2, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Following clinical recovery from initial myeloablative therapy, patients also receive melphalan, etoposide, and carboplatin as in Arm A. Patients undergo autologous PBSCT on day 0.


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

Treatment: Drugs: Carboplatin
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

Other interventions: Filgrastim
Given IV or SC

Treatment: Drugs: Isotretinoin
Given orally

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Melphalan
Given IV

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

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Thiotepa
Given IV

Treatment: Drugs: Topotecan Hydrochloride
Given IV

Treatment: Drugs: Vincristine Sulfate Liposome
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
Event-free Survival Rate - Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM)
Timepoint [1] 0 0
Three years, from time of randomization
Primary outcome [2] 0 0
Incidence Rate of Local Recurrence - Cumulative incidence rate of local recurrence comparison between ANBL0532 patients randomized or assigned to receive single CEM transplant and boost radiation versus the historical A3973 patients who were transplanted and received boost radiation.
Timepoint [2] 0 0
Up to 3 years
Primary outcome [3] 0 0
Response After Induction Therapy - Per the International Response Criteria: measurable tumor defined as product of longest x widest perpendicular diameter. Elevated catecholamine levels, tumor cell invasion of bone marrow also considered measurable tumor. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)->90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; >50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by >50%. Mixed Response (MR)->50% reduction of any measurable lesion (primary or metastases) with <50% reduction in other sites; no new lesions; <25% increase in any existing lesion. No Response (NR)-no new lesions; <50% reduction but <25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by >25%; previous negative marrow positive.
Timepoint [3] 0 0
Study enrollment to the end of induction therapy
Secondary outcome [1] 0 0
Duration of Greater Than or Equal to Grade 3 Neutropenia - A logistic regression model will be used to test the ability of the number of days of neutropenia to predict the presence of a polymorphism.
Timepoint [1] 0 0
21 days
Secondary outcome [2] 0 0
Duration of Greater Than or Equal to Grade 3 Thrombocytopenia - A logistic regression model will be used to test the ability of the number of days of thrombocytopenia to predict the presence of a polymorphism.
Timepoint [2] 0 0
21 days
Secondary outcome [3] 0 0
EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology). - Kaplan-Meier curves of EFS will be plotted, and the proportion of responders to induction therapy will be tabulated.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells - A descriptive comparison of the median number of T-cells (CD3, CD4, CD8) between treatment arms (single vs. tandem myeloablative regimens) will be performed.
Timepoint [4] 0 0
Up to 6 months after completion of assigned myeloablation therapy
Secondary outcome [5] 0 0
Intraspinal Extension - Proportion of patients with primary tumors with intraspinal extension.
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology - Kaplan-Meier curves of OS will be plotted, and the proportion of responders to induction therapy will be tabulated.
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies - Median peak serum concentration level of isotretinoin for patients enrolled on ANBL0532
Timepoint [7] 0 0
Day 1 of each course
Secondary outcome [8] 0 0
Pharmacogenetic Variants in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies - To determine if pharmacogenomic variations are predictive of EFS, a logrank test comparison of patients with vs without a given polymorphism will be made. A Fisher's exact test will test for association of the presence of a polymorphism with the occurrence of systemic toxicity (CTC grade 3 or 4 skin, hypercalcemia, or hepatic toxicity). These tests will be performed for UGT1A1, UGT2B7, CYP2C8 and CYP3A7 alleles.
Timepoint [8] 0 0
Baseline
Secondary outcome [9] 0 0
Presence and Function of T Cells Capable of Recognizing Neuroblastoma
Timepoint [9] 0 0
Up to 6 months (end of therapy)
Secondary outcome [10] 0 0
Proportion of Patients With Neuroblastoma Detected in Bone Marrow and Peripheral Blood Using RT-PCR Technique - Will be calculated overall and by treatment arm.
Timepoint [10] 0 0
Baseline
Secondary outcome [11] 0 0
Response Rate - A chi-square test of association will be used to compare the proportion of responders with versus without a polymorphism.
Timepoint [11] 0 0
42 days
Secondary outcome [12] 0 0
Surgical Response - Proportion of patients who achieved a surgical complete resection
Timepoint [12] 0 0
Up to 3 years
Secondary outcome [13] 0 0
Topotecan Systemic Clearance - Median topotecan systemic clearance for courses 1 and 2.
Timepoint [13] 0 0
Day 1 of courses 1-2
Secondary outcome [14] 0 0
Type of Surgical or Radiotherapy Complication - The proportion of patients who experienced surgical or radiotherapy complications will be calculated. The complications are: bowel obstruction, chylous leaf, renal injury/atrophy/loss and diarrhea.
Timepoint [14] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
- Diagnosis of neuroblastoma or ganglioneuroblastoma by histology or as evidenced by the
presence of clumps of tumor cells in bone marrow and elevated catecholamine
metabolites in urine meeting any of the following criteria:

- Patients with newly diagnosed neuroblastoma with International Neuroblastoma
Staging System (INSS) stage 4 disease are eligible with the following:

- MYCN amplification (i.e., greater than four-fold increase in MYCN signals as
compared to reference signals), regardless of age or additional biologic
features

- Age > 18 months (i.e., > 547 days) regardless of biologic features

- Age 12-18 months (i.e., 365-547 days) with none of the following three
favorable biologic features (i.e., non-amplified MYCN, favorable pathology,
and deoxyribonucleic acid [DNA] index > 1)

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

- MYCN amplification (i.e., greater than four-fold increase in MYCN signals as
compared to reference signals), regardless of age or additional biologic
features

- Age > 18 months (i.e., > 547 days) with unfavorable pathology, regardless of
MYCN status

- Patients with newly diagnosed INSS stage 2a or 2b with MYCN amplification (i.e.,
greater than four-fold increase in MYCN signals as compared to reference
signals), regardless of age or additional biologic features

- Patients with newly diagnosed INSS stage 4s with MYCN amplification (i.e.,
greater than four-fold increase in MYCN signals as compared to reference
signals), regardless of additional biologic features

- Patients >= 365 days initially diagnosed with INSS stage 1, 2, or 4S and who
progressed to a stage 4 without interval chemotherapy

- Must have been enrolled on COG-ANBL00B1

- Creatinine clearance or radioisotope glomerular filtration rate ? 70mL/min OR serum
creatinine based on age/gender as follows:

- 1 month to < 6 months: 0.4 mg/dL

- 6 months to < 1 year: 0.5 mg/dL

- 1 to < 2 years: 0.6 mg/dL

- 2 to < 6 years: 0.8 mg/dL

- 6 to < 10 years: 1 mg/dL

- 10 to < 13 years: 1.2 mg/dL

- 10 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)

- >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)

- Total bilirubin ? 1.5 times upper limit of normal (ULN) for age

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 10 times ULN for
age

- Not pregnant or nursing

- Negative pregnancy test

- Shortening fraction >= 27% by echocardiogram (ECHO) OR left ventricular ejection
fraction (LVEF) >= 50% by radionuclide angiogram

- No known contraindication (e.g., size, weight or physical condition) to peripheral
blood stem cell collection

- No prior systemic therapy except for localized emergency radiation to sites of
life-threatening or function-threatening disease

- No more than one course of chemotherapy per low- or intermediate-risk neuroblastoma
therapy prior to determination of MYCN amplification and histology
Minimum age
No limit
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
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Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
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Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maine
Country [18] 0 0
United States of America
State/province [18] 0 0
Maryland
Country [19] 0 0
United States of America
State/province [19] 0 0
Massachusetts
Country [20] 0 0
United States of America
State/province [20] 0 0
Michigan
Country [21] 0 0
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State/province [21] 0 0
Minnesota
Country [22] 0 0
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Mississippi
Country [23] 0 0
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State/province [23] 0 0
Missouri
Country [24] 0 0
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State/province [24] 0 0
Nebraska
Country [25] 0 0
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Nevada
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State/province [26] 0 0
New Hampshire
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New Jersey
Country [28] 0 0
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State/province [28] 0 0
New Mexico
Country [29] 0 0
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State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
State/province [36] 0 0
South Carolina
Country [37] 0 0
United States of America
State/province [37] 0 0
South Dakota
Country [38] 0 0
United States of America
State/province [38] 0 0
Tennessee
Country [39] 0 0
United States of America
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Texas
Country [40] 0 0
United States of America
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Utah
Country [41] 0 0
United States of America
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Vermont
Country [42] 0 0
United States of America
State/province [42] 0 0
Virginia
Country [43] 0 0
United States of America
State/province [43] 0 0
Washington
Country [44] 0 0
United States of America
State/province [44] 0 0
West Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Wisconsin
Country [46] 0 0
Canada
State/province [46] 0 0
Alberta
Country [47] 0 0
Canada
State/province [47] 0 0
British Columbia
Country [48] 0 0
Canada
State/province [48] 0 0
Manitoba
Country [49] 0 0
Canada
State/province [49] 0 0
Nova Scotia
Country [50] 0 0
Canada
State/province [50] 0 0
Ontario
Country [51] 0 0
Canada
State/province [51] 0 0
Quebec
Country [52] 0 0
New Zealand
State/province [52] 0 0
Auckland
Country [53] 0 0
Puerto Rico
State/province [53] 0 0
San Juan
Country [54] 0 0
Switzerland
State/province [54] 0 0
Bern

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
This randomized phase III trial compares two different high-dose chemotherapy regimens
followed by a stem cell transplant in treating younger patients with high-risk neuroblastoma.
Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either
by killing the cells or by stopping them from dividing. Giving combination chemotherapy
before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
to be removed. Giving these treatments before a peripheral blood stem cell transplant helps
kill any tumor cells that are in the body and helps make room in the patient?s bone marrow
for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected
from the patient's blood and stored. High-dose chemotherapy and radiation therapy is then
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 high-
chemotherapy. It is not yet known which regimen of high-dose chemotherapy is more effective
for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.
Trial website
https://clinicaltrials.gov/show/NCT00567567
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Julie R Park
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

Summary results
Other publications