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Trial record 7 of 7 for:    stem cell kidney | ( Map: Switzerland )

Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00567567
Recruitment Status : Completed
First Posted : December 5, 2007
Results First Posted : June 27, 2017
Last Update Posted : May 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE December 4, 2007
First Posted Date  ICMJE December 5, 2007
Results First Submitted Date  ICMJE January 20, 2017
Results First Posted Date  ICMJE June 27, 2017
Last Update Posted Date May 1, 2019
Actual Study Start Date  ICMJE November 5, 2007
Actual Primary Completion Date February 27, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2017)
  • Event-free Survival Rate [ Time Frame: Three years, from time of randomization ]
    Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM)
  • Incidence Rate of Local Recurrence [ Time Frame: Up to 3 years ]
    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.
  • Response After Induction Therapy [ Time Frame: Study enrollment to the end of 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2007)
  • Event-free Survival Rate
  • Response after induction therapy
  • Incidence Rate of Local Recurrence
Change History Complete list of historical versions of study NCT00567567 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Duration of Greater Than or Equal to Grade 3 Neutropenia [ Time Frame: 21 days ]
    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.
  • Duration of Greater Than or Equal to Grade 3 Thrombocytopenia [ Time Frame: 21 days ]
    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.
  • 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). [ Time Frame: Up to 3 years ]
    Kaplan-Meier curves of EFS will be plotted, and the proportion of responders to induction therapy will be tabulated.
  • Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells [ Time Frame: Up to 6 months after completion of assigned myeloablation therapy ]
    A descriptive comparison of the median number of T-cells (CD3, CD4, CD8) between treatment arms (single vs. tandem myeloablative regimens) will be performed.
  • Intraspinal Extension [ Time Frame: Up to 5 years ]
    Proportion of patients with primary tumors with intraspinal extension.
  • 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 [ Time Frame: Up to 3 years ]
    Kaplan-Meier curves of OS will be plotted, and the proportion of responders to induction therapy will be tabulated.
  • Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies [ Time Frame: Day 1 of each course ]
    Median peak serum concentration level of isotretinoin for patients enrolled on ANBL0532
  • Pharmacogenetic Variants in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies [ Time Frame: Baseline ]
    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.
  • Presence and Function of T Cells Capable of Recognizing Neuroblastoma [ Time Frame: Up to 6 months (end of therapy) ]
  • Proportion of Patients With Neuroblastoma Detected in Bone Marrow and Peripheral Blood Using RT-PCR Technique [ Time Frame: Baseline ]
    Will be calculated overall and by treatment arm.
  • Response Rate [ Time Frame: 42 days ]
    A chi-square test of association will be used to compare the proportion of responders with versus without a polymorphism.
  • Surgical Response [ Time Frame: Up to 3 years ]
    Proportion of patients who achieved a surgical complete resection
  • Topotecan Systemic Clearance [ Time Frame: Day 1 of courses 1-2 ]
    Median topotecan systemic clearance for courses 1 and 2.
  • Type of Surgical or Radiotherapy Complication [ Time Frame: Up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2007)
  • Duration of ≥ grade 3 neutropenia during course one
  • Duration of ≥ grade 3 thrombocytopenia during course one
  • Response rate after two courses of induction therapy
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
Official Title  ICMJE Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma
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.
Detailed Description

PRIMARY OBJECTIVES:

I. To improve the 3-year event-free survival (EFS) rate of high-risk neuroblastoma patients through treatment with a tandem consolidation of thiotepa/cyclophosphamide followed by carboplatin/etoposide/melphalan (CEM) as compared to single CEM consolidation.

II. To improve the rate of end-induction complete response and very good partial response, compared to historical controls, by use of a topotecan-containing induction regimen.

III. To improve the 3-year local control rate, compared to historical controls, by increasing the local dose of radiation to the residual primary tumor for patients with less than a gross total resection.

SECONDARY OBJECTIVES:

I. To evaluate the pharmacogenetic relationship of cyclophosphamide metabolizing enzymes (CYP2B6, CYP2C9, and GSTA1 genotypes) with toxicity and response following dose-intensive cyclophosphamide and topotecan induction chemotherapy.

II. To determine if resection completeness is predictive of a) local control rate; or b) EFS rate in patients with high-risk neuroblastoma.

III. To prospectively describe the complications related to efforts at local control (surgery and radiation therapy) in patients with high-risk neuroblastoma.

IV. To describe the neurologic outcome of patients with paraspinal primary neuroblastoma tumors.

V. To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters and determine if pharmacokinetics and/or genetic variations correlate with EFS or systemic toxicity as follows: a) To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters. b) To determine if 13-cis-retinoic-acid pharmacokinetic levels are predictive of the EFS rate or associated with systemic toxicity following 13-cis-retinoic acid. c) To determine if pharmacogenomic variations are predictive of the EFS rate or associated with systemic toxicity following 13-cis-retinoic acid.

VI. To evaluate total topotecan pharmacokinetics and correlate with patient specific data for use in an ongoing topotecan population pharmacokinetic analysis.

VII. To evaluate the presence and function of T cells capable of recognizing neuroblastoma by assessing: a) if T cells recognizing the neuroblastoma antigen, survivin, circulate at diagnosis; b) if these T cells can be expanded using autologous antigen presenting cells (APCs); c) if these T cells will kill neuroblastoma cells as detected in functional assays; and d) if the presence and activity of anti-neuroblastoma immunity is decreased by stem cell transplantation.

VIII. To characterize the recovery of T- cell numbers after myeloablative consolidation and hematopoietic stem cell transplant (HSCT) and assess the impact of tandem myeloablative consolidation on T- cell recovery.

IX. To characterize minimal residual disease burden using reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation of a panel of neuroblastoma specific transcripts in patient bone marrow and peripheral blood following induction chemotherapy and after single versus tandem myeloablative chemotherapy and to evaluate impact on EFS.

X. To evaluate the EFS and overall survival (OS) rate for patients 12-18 months with Stage 4, MYCN nonamplified tumor with unfavorable histopathology or diploid DNA content or with indeterminant histology or ploidy and patients who are greater than 547 days of age with Stage 3, MYCN nonamplified tumor AND unfavorable histopathology or indeterminant histology following treatment with single myeloablative transplant.

OUTLINE:

INDUCTION CHEMOTHERAPY:

COURSES 1 AND 2: Patients receive cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients undergo peripheral blood stem cell (PBSC) mobilization and harvest after course 2.

COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4, etoposide IV over 1 hour on days 1-3, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients undergo surgical resection of soft tissue disease after course 5 (or after course 6 if medically necessary).

COURSES 4 AND 6: Patients receive cyclophosphamide IV over 6 hours on days 1-2, doxorubicin hydrochloride IV over 24 hours on days 1-3, vincristine IV on days 1-3, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses.

Patients are then stratified by initial stage of disease and MYCN status, biologic characteristics, and response to induction chemotherapy (complete response/very good partial response vs partial response vs mixed response/no response). Patients are randomized to 1 of 2 arms. Patients 12?18 months old (i.e., 365-547 days) with stage IV, MYCN nonamplified tumor with unfavorable histopathology or diploid DNA content or with indeterminant histology or ploidy AND patients who are 547 days of age with stage III, MYCN nonamplified tumor AND unfavorable histopathology or indeterminant histology will be nonrandomly assigned to Arm A. Patients begin consolidation chemotherapy no later than 8 weeks after the start of induction course 6.

CONSOLIDATION THERAPY:

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 peripheral blood stem cell transplant (PBSCT) on day 0.

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.

RADIOTHERAPY: Patients undergo external beam radiation therapy (EBRT) to primary site of disease as well as to MIBG-avid sites seen at pre-transplantation (i.e., end-induction) evaluation between 28-42 days post-transplant. Additional radiotherapy is administered to residual tumor at primary site.

MAINTENANCE THERAPY: Patients are encouraged to enroll onto Children?s Oncology Group (COG)-ANBL0032 following assessment of tumor response after completion of the consolidation phase and radiotherapy. Beginning on day 60 post-transplantation patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood and tissue sample collection periodically for the following analyses; correlation between peak serum concentration level and the existence of polymorphisms, event-free survival, and toxicity rates; pharmacogenomics for uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), UGT2B7, CYP2C8 and CYP3A7 alleles; topotecan systemic clearance; survivin-specific cytotoxic T-lymphocytes (CTLs) detected using peptide/major histocompatibility complex (MHC) tetramers in human leukocyte antigen (HLA)-A2+ patients; interferon (IFN)-gamma production in enzyme-linked immunospot (ELISPOT) assays to APCs loaded with tumor ribonucleic acid (RNA), survivin RNA, or control RNA; response of APC-stimulated CTL response to neuroblastoma cells; rate of T cell recovery; and proportion of patients with neuroblastoma detected in bone marrow and peripheral blood using RT-PCR and immunohistochemistry (IHC).

After completion of study treatment, patients are followed up periodically for 5 years and then annually for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Recurrent Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4 Neuroblastoma
  • Stage 4S Neuroblastoma
Intervention  ICMJE
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    Undergo autologous peripheral blood stem cell transplant
    Other Names:
    • Autologous Hematopoietic Cell Transplantation
    • autologous stem cell transplantation
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other Names:
    • 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
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
    • 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
    • Doxorubin
    • Farmiblastina
    • FI 106
    • FI-106
    • hydroxydaunorubicin
    • Rubex
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Radiation: External Beam Radiation Therapy
    Undergo EBRT
    Other Names:
    • Definitive Radiation Therapy
    • EBRT
    • External Beam Radiotherapy
    • External Beam RT
    • external radiation
    • External Radiation Therapy
    • external-beam radiation
  • Biological: Filgrastim
    Given IV or SC
    Other Names:
    • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
    • G-CSF
    • Neupogen
    • r-metHuG-CSF
    • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
    • rG-CSF
    • Tevagrastim
  • Drug: Isotretinoin
    Given orally
    Other Names:
    • 13-cis retinoic acid
    • 13-cis-Retinoate
    • 13-cis-Retinoic Acid
    • 13-cis-Vitamin A Acid
    • 13-cRA
    • Accure
    • Accutane
    • Amnesteem
    • cis-Retinoic Acid
    • Cistane
    • Claravis
    • Isotretinoinum
    • Isotrex
    • Isotrexin
    • Neovitamin A
    • Neovitamin A Acid
    • Oratane
    • Retinoicacid-13-cis
    • Ro 4-3780
    • Ro-4-3780
    • Roaccutan
    • Roaccutane
    • Roacutan
    • Sotret
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Melphalan
    Given IV
    Other Names:
    • Alanine Nitrogen Mustard
    • CB-3025
    • L-PAM
    • L-Phenylalanine Mustard
    • L-sarcolysin
    • L-Sarcolysin Phenylalanine mustard
    • L-Sarcolysine
    • Melphalanum
    • Phenylalanine Mustard
    • Phenylalanine nitrogen mustard
    • Sarcoclorin
    • Sarkolysin
    • WR-19813
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo autologous peripheral blood stem cell transplant
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplant
    • Peripheral Stem Cell Transplantation
  • Other: Pharmacological Study
    Correlative studies
  • Drug: Thiotepa
    Given IV
    Other Names:
    • 1,1',1''-Phosphinothioylidynetrisaziridine
    • Girostan
    • N,N', N''-Triethylenethiophosphoramide
    • Oncotiotepa
    • STEPA
    • Tepadina
    • TESPA
    • Tespamin
    • Tespamine
    • Thio-Tepa
    • Thiofosfamide
    • Thiofozil
    • Thiophosphamide
    • Thiophosphoramide
    • Thiotef
    • Tifosyl
    • TIO TEF
    • Tio-tef
    • Triethylene thiophosphoramide
    • Triethylenethiophosphoramide
    • Tris(1-aziridinyl)phosphine sulfide
    • TSPA
    • WR 45312
  • Drug: Topotecan Hydrochloride
    Given IV
    Other Names:
    • Hycamptamine
    • Hycamtin
    • SKF S-104864-A
    • Topotecan HCl
    • topotecan hydrochloride (oral)
  • Drug: Vincristine Sulfate Liposome
    Given IV
    Other Name: Marqibo
Study Arms  ICMJE
  • 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.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide
    • Radiation: External Beam Radiation Therapy
    • Biological: Filgrastim
    • Drug: Isotretinoin
    • Other: Laboratory Biomarker Analysis
    • Drug: Melphalan
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Other: Pharmacological Study
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate Liposome
  • 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.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide
    • Radiation: External Beam Radiation Therapy
    • Biological: Filgrastim
    • Drug: Isotretinoin
    • Other: Laboratory Biomarker Analysis
    • Drug: Melphalan
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Other: Pharmacological Study
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate Liposome
Publications * Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. JAMA. 2019 Aug 27;322(8):746-755. doi: 10.1001/jama.2019.11642.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 18, 2019)
630
Original Enrollment  ICMJE
 (submitted: December 4, 2007)
495
Actual Study Completion Date  ICMJE February 27, 2015
Actual Primary Completion Date February 27, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland,   Australia,   Canada,   New Zealand,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00567567
Other Study ID Numbers  ICMJE ANBL0532
NCI-2009-01065 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000576571
08-524
COG-ANBL0532
ANBL0532 ( Other Identifier: Childrens Oncology Group )
ANBL0532 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Julie R Park Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP