Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03126916
Recruitment Status : Active, not recruiting
First Posted : April 25, 2017
Last Update Posted : February 4, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE April 17, 2017
First Posted Date  ICMJE April 25, 2017
Last Update Posted Date February 4, 2021
Actual Study Start Date  ICMJE May 9, 2018
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2019)
Event free survival (EFS) (Arm A, B, D, and E) [ Time Frame: 3 years ]
EFS time is calculated from date of randomization or assignment to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
EFS rate [ Time Frame: From the time of randomization or assignment to first episode of disease relapse or progression, first occurrence of a second malignancy, or death, assessed for up to 5 years ]
Will be assessed with an intent-to-treat log-rank test comparison of EFS rates. The EFS of patients assigned to the ALK-aberrant crizotinib treatment arm will be compared with an intent-to-treat log-rank test to that of all patients assigned to the ALK wild type portion of the trial, except for those patients randomized to receive 131I-MIBG.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2019)
  • Incidence of adverse events [ Time Frame: Up to 18 months for Arms A-D and 28 months for Arm E ]
    The proportion of patients with at least one Grade 3 or higher toxicity during protocol therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, will be reported.
  • EFS (Arm C) [ Time Frame: 3 years ]
    EFS time is calculated from date of randomization to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
  • Overall survival (OS) [ Time Frame: 3 years ]
    OS time is calculated from date of randomization or assignment until death, or until last contact if patient is alive.
  • Response rate [ Time Frame: Up to 6 months ]
    The response rate will be calculated among all evaluable patients at end-Induction. Responders are defined as patients who achieve a >= partial response (PR) per the revised International Neuroblastoma Response Criteria (INRC).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria version 4.0 [ Time Frame: Up to 5 years ]
    Will use chi-squared tests to determine incremental increases in toxicity that result from the addition of crizotinib. Separate comparisons for Induction, Consolidation, post-Consolidation (with immunotherapy and with crizotinib monotherapy), and follow-up phases will be performed. Chi-squared and Wilcoxon rank-sum tests will be used to assess incremental increases in toxicity from the addition of 131I-MIBG.
  • Non-inferiority of 131I-MIBG plus BuMel and 131I-MIBG plus tandem transplant [ Time Frame: Up to 5 years ]
    The 131I-MIBG plus BuMel arm will be compared to the 131I-MIBG plus tandem transplant arm, and success will be declared and the 131I-MIBG plus BuMel arm deemed non-inferior to the 131I-MIBG plus tandem transplant arm if the upper boundary of the two-sided 90% confidence interval for the hazard ratio from a Cox proportional hazards model is less than 1.3.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 24, 2017)
  • Overall Survival Rate [ Time Frame: From the time of randomization, or assignment to the crizotinib arm until death, assessed for up to 5 years ]
    A log-rank test will be used to compare OS rates of patients randomized to receive 131I-MIBG plus tandem transplant and those randomized to tandem transplant only. Depending on the sample size at each time point, a chi-square or Fisher's exact test will be used to evaluate the difference in end-Induction, post-Consolidation, and end of therapy response rates in these groups. OS and response rates of patients treated with crizotinib and those comprising the comparator group will also be evaluated.
  • Response assessed by the International Neuroblastoma Response Criteria [ Time Frame: Up to 5 years ]
    Log-rank tests will be used to compare EFS and OS rates of patients classified according to INRC response category. Analyses will be performed focusing on the entire trial cohort and separately for Arms A, B, and E.
 
Descriptive Information
Brief Title  ICMJE Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma
Official Title  ICMJE A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)
Brief Summary This phase III trial studies iobenguane I-131 or crizotinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or crizotinib and standard therapy may work better compared to crizotinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine in the context of a randomized trial whether the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma (NBL) is improved with the addition of iobenguane I-131 (131I-MIBG) during induction, prior to tandem autologous stem cell transplantation (ASCT).

II. To determine whether the addition of crizotinib to intensive multimodality therapy for patients with high-risk NBL whose tumors harbor activating point mutations in or amplification of the ALK gene results in superior EFS compared to a contemporaneously treated cohort of patients whose tumors lack these ALK aberrations.

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with treatment for high-risk NBL with and without the addition of 131I-MIBG or crizotinib.

II. To estimate EFS and describe toxicity in patients with newly diagnosed high-risk NBL randomized to treatment with an 131I-MIBG-containing induction prior to busulfan/melphalan (BuMel) ASCT.

III. To describe the overall survival (OS) and response rates (evaluated per International Neuroblastoma Response Criteria [INRC] criteria prior to ASCT and prior to post-consolidation therapy) for patients with high-risk neuroblastoma treated with or without 131I-MIBG or crizotinib.

IV. To prospectively evaluate the relationship of response rate per revised International Neuroblastoma Response Criteria (INRC) to EFS and OS in patients with high-risk NBL treated with and without the addition of 131I-MIBG or crizotinib.

EXPLORATORY OBJECTIVES:

I. To evaluate whole body radiation dose, tumor factors, and host factors as potential predictors of efficacy and/or toxicity associated with 131I-MIBG therapy and transplant conditioning.

II. To determine whether the efficacy (end-induction response, EFS, and OS) of crizotinib is associated with specific ALK mutations or ALK amplification.

III. To characterize changes in tumor markers (circulating tumor deoxyribonucleic acid [DNA], including ALK and other tumor specific genetic aberrations, and circulating GD2) over time in response to protocol therapy.

IV. To correlate results of tumor and host profiling with end-induction response and EFS.

V. To prospectively evaluate EFS for patients with MIBG non-avid high-risk NBL compared to patients with MIBG-avid high-risk NBL who are randomized to treatment without 131I-MIBG.

VI. To correlate Curie scores calculated from 131I-MIBG post-treatment scans with end-induction response, EFS and OS.

VII. To describe changes in image defined risk factors (IDRFs) over the course of induction therapy, with correlation to surgical outcomes and local failure rates following primary tumor resection.

VIII. To define patterns of failure at time of first relapse or progression in patients with high-risk NBL.

IX. To determine the feasibility of prospectively monitoring adverse events using electronic health records.

X. To compare local, central, and computer assisted Curie score assignment at baseline and during therapy in patients with MIBG-avid high-risk NBL.

XI. To compare late toxicities (including impaired organ function and secondary tumor occurrence) in patients treated with 131I-MIBG or crizotinib to late toxicities in patients who have not received these therapies.

XII. To determine the association between household material hardship (HMH) and clinical outcomes, including event free and overall survival, and 131I-MIBG receipt.

XIII. To compare the outcomes (EFS, OS, and toxicity) of patients treated with post-consolidation therapy that does not contain aldesleukin to historical outcome data for patients treated with similar induction and consolidation regimens followed by post-consolidation therapy that contained aldesleukin.

OUTLINE: Patients are randomized or assigned to 1 of 5 arms.

All patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 during cycle 1 of induction therapy in the absence of disease progression or unacceptable toxicity. Patients not assigned to an Arm by the end of cycle 1 may receive an addition cycle of cyclophosphamide and topotecan.

ARM A:

INDUCTION THERAPY: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 of cycle 2 and cisplatin IV over 4 hours and etoposide phosphate IV over 2 hours on days 1-3 of cycles 3 and 5. Patients also receive vincristine sulfate IV over 1 minute on day 1 and dexrazoxane hydrochloride IV over 5-15 minutes, doxorubicin hydrochloride IV over 1-15 minutes, and cyclophosphamide IV over 1-6 hours on days 1-2 of cycle 4 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY:

HSCT#1: Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2 in the absence of disease progression or unacceptable toxicity.

HSCT#2: Patients receive melphalan hydrochloride IV over 30 minutes on days -7 to -5, and etoposide phosphate IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4 in the absence of disease progression or unacceptable toxicity.

POST-CONSOLIDATION THERAPY: Patients receive sargramostim subcutaneously (SC) on days 1-14, dinutuximab IV over 10 hours on days 4-7 of cycles 1-5, and isotretinoin orally (PO) twice daily (BID) on days 11-24 of cycles 1-5, and days 15-28 during cycle 6 in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION THERAPY: Patients receive cyclophosphamide, topotecan hydrochloride, cisplatin, and etoposide phosphate as in Arm A, iobenguane I-131 IV over 1.5-2 hours on day 1 beginning 3 weeks after the start of cycle 3, and vincristine sulfate, dexrazoxane hydrochloride, doxorubicin hydrochloride, and cyclophosphamide as in Arm A beginning no sooner than 35 days after the infusion of iobenguane I-131.

CONSOLIDATION THERAPY:

HSCT#1: Patients receive thiotepa and cyclophosphamide as in Arm A.

HSCT#2: Patients receive melphalan, etoposide phosphate, and carboplatin as in Arm A.

POST-CONSLIDATION THERAPY: Patients receive sargramostim, dinutuximab, and isotretinoin as in Arm A-D.

ARM C:

INDUCTION THERAPY: Patients receive cyclophosphamide, topotecan hydrochloride, cisplatin, etoposide phosphate, iobenguane I-131, vincristine sulfate, dexrazoxane hydrochloride, doxorubicin hydrochloride, and cyclophosphamide as in Arm B.

CONSOLIDATION THERAPY: Patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan hydrochloride IV over 30 minutes on day -1 in the absence of disease progression or unacceptable toxicity.

POST-CONSOLIDATION THERAPY: Patients receive sargramostim, dinutuximab, and isotretinoin as in Arm A.

ARM D: Patients receive treatment identical to Arm A.

ARM E:

INDUCTION THERAPY: Patients receive cyclophosphamide, topotecan hydrochloride, cisplatin, etoposide phosphate, vincristine sulfate, dexrazoxane hydrochloride, doxorubicin hydrochloride, and cyclophosphamide as in Arm A. Patients also receive crizotinib PO BID on days 1-21 of cycles 2-4 and days 1-8 of cycle 5 prior to HSCT #1 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY:

HSCT#1: Patients receive thiotepa and cyclophosphamide as in Arm A. Patients also receive crizotinib PO BID until day -8 of HSCT#2 in the absence of disease progression or unacceptable toxicity.

HSCT#2: Patients receive melphalan hydrochloride, etoposide phosphate, carboplatin as in Arm A. Crizotinib is restarted when external beam radiation is initiated, provided there is no evidence of disease progression or unacceptable toxicity.

POST-CONSOLIDATION THERAPY: Patients receive sargramostim and dinutuximab as in Arm A-D. Patients also receive isotretinoin PO BID on days 11-24 of cycles 1-5 and days 15-28 of cycle 6, and crizotinib PO BID on days 1-28 of cycles 1-6 in the absence of disease progression or unacceptable toxicity.

CONTINUATION THERAPY: Patients receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients in Arms A-D are followed up every 3 months for 18 months, and then every 6 months for 42 months; patients in Arm E are followed up every 3 months for 6 months, and then every 6 months for 42 months.

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
  • Ganglioneuroblastoma
  • INRG Stage L2
  • INRG Stage M
  • INRG Stage MS
  • Neuroblastoma
Intervention  ICMJE
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    Undergo autologous HSCT
    Other Names:
    • AHSCT
    • Autologous
    • Autologous Hematopoietic Cell Transplantation
    • Autologous Stem Cell Transplant
    • Autologous Stem Cell Transplantation
    • Stem Cell Transplantation, Autologous
  • Drug: Busulfan
    Given IV
    Other Names:
    • 1, 4-Bis[methanesulfonoxy]butane
    • BUS
    • 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
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • 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: Crizotinib
    Given PO
    Other Names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • 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
    • Cyclophosphamide Monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Drug: Dexrazoxane Hydrochloride
    Given IV
    Other Names:
    • Cardioxane
    • Totect
    • Zinecard
  • Biological: Dinutuximab
    Given IV
    Other Names:
    • Ch 14.18UTC
    • Ch14.18
    • MOAB Ch14.18
    • monoclonal antibody Ch14.18
    • Unituxin
  • 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
    • Doxorubicin.HCl
    • Doxorubin
    • Farmiblastina
    • FI 106
    • FI-106
    • hydroxydaunorubicin
    • Rubex
  • Drug: Etoposide Phosphate
    Given IV
    Other Name: Etopophos
  • Radiation: External Beam Radiation Therapy
    Undergo EBRT
    Other Names:
    • Definitive Radiation Therapy
    • EBRT
    • External Beam Radiation
    • External Beam Radiotherapy
    • External Beam RT
    • external radiation
    • External Radiation Therapy
    • external-beam radiation
    • Radiation, External Beam
  • Radiation: Iobenguane I-131
    Given IV
    Other Names:
    • (131)I-MIBG
    • 131I-MIBG
    • I 131 Meta-iodobenzylguanidine
    • I-131 Metaiodobenzylguanidine
    • Iobenguane (131I)
    • Iobenguane I 131
    • Iodine I 131 Metaiodobenzylguanidine
    • MIBG I-131
  • Drug: Isotretinoin
    Given PO
    Other Names:
    • 13-cis retinoic acid
    • 13-cis-Retinoate
    • 13-cis-Retinoic Acid
    • 13-cis-Vitamin A Acid
    • 13-cRA
    • Absorica
    • Accure
    • Accutane
    • Amnesteem
    • cis-Retinoic Acid
    • Cistane
    • Claravis
    • Isotretinoinum
    • Isotrex
    • Isotrexin
    • Myorisan
    • Neovitamin A
    • Neovitamin A Acid
    • Oratane
    • Retinoicacid-13-cis
    • Ro 4-3780
    • Ro-4-3780
    • Roaccutan
    • Roaccutane
    • Roacutan
    • Sotret
    • ZENATANE
  • Drug: Melphalan Hydrochloride
    Given IV
    Other Names:
    • Alkeran
    • Alkerana
    • Evomela
  • Biological: Sargramostim
    Given SC
    Other Names:
    • 23-L-Leucinecolony-Stimulating Factor 2
    • DRG-0012
    • Leukine
    • Prokine
    • rhu GM-CFS
    • Sagramostim
    • Sargramostatin
  • Procedure: Therapeutic Conventional Surgery
    Undergo standard of care surgery
  • 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
    Given IV
    Other Names:
    • Kyocristine
    • Leurocristine Sulfate
    • Leurocristine, sulfate
    • Oncovin
    • Vincasar
    • Vincosid
    • Vincrex
    • Vincristine, sulfate
Study Arms  ICMJE
  • Experimental: Arm A (chemotherapy, HSCT, EBRT)
    See Arm A in detailed description.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Dexrazoxane Hydrochloride
    • Biological: Dinutuximab
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide Phosphate
    • Radiation: External Beam Radiation Therapy
    • Drug: Isotretinoin
    • Biological: Sargramostim
    • Procedure: Therapeutic Conventional Surgery
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate
  • Experimental: Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    See Arm B in detailed description.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Dexrazoxane Hydrochloride
    • Biological: Dinutuximab
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide Phosphate
    • Radiation: External Beam Radiation Therapy
    • Radiation: Iobenguane I-131
    • Drug: Isotretinoin
    • Biological: Sargramostim
    • Procedure: Therapeutic Conventional Surgery
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate
  • Experimental: Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    See Arm C in detailed description.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Busulfan
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Dexrazoxane Hydrochloride
    • Biological: Dinutuximab
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide Phosphate
    • Radiation: External Beam Radiation Therapy
    • Radiation: Iobenguane I-131
    • Drug: Isotretinoin
    • Drug: Melphalan Hydrochloride
    • Biological: Sargramostim
    • Procedure: Therapeutic Conventional Surgery
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate
  • Experimental: Arm D (chemotherapy, HSCT, EBRT)
    See Arm D in detailed description.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Cyclophosphamide
    • Drug: Dexrazoxane Hydrochloride
    • Biological: Dinutuximab
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide Phosphate
    • Radiation: External Beam Radiation Therapy
    • Drug: Isotretinoin
    • Biological: Sargramostim
    • Procedure: Therapeutic Conventional Surgery
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
    • Drug: Vincristine Sulfate
  • Experimental: Arm E (crizotinib, chemotherapy, HSCT, EBRT)
    See Arm E in detailed description.
    Interventions:
    • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Crizotinib
    • Drug: Cyclophosphamide
    • Drug: Dexrazoxane Hydrochloride
    • Biological: Dinutuximab
    • Drug: Doxorubicin Hydrochloride
    • Drug: Etoposide Phosphate
    • Radiation: External Beam Radiation Therapy
    • Drug: Isotretinoin
    • Biological: Sargramostim
    • Procedure: Therapeutic Conventional Surgery
    • Drug: Thiotepa
    • Drug: Topotecan Hydrochloride
Publications * Not Provided

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2019)
813
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2017)
774
Estimated Study Completion Date  ICMJE September 30, 2026
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531
  • Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:

    • Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
      • Age > 547 days regardless of biologic features
    • Patients with INRG stage MS disease with MYCN amplification
    • Patients with INRG stage L2 disease with MYCN amplification
    • Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
    • Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
  • Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

    • 1 to < 2 years: male = 0.6; female = 0.6
    • 2 to < 6 years: male = 0.8; female = 0.8
    • 6 to < 10 years: male = 1; female = 1
    • 10 to < 13 years: male = 1.2; female = 1.2
    • 13 to < 16 years: male = 1.5; female = 1.4
    • >= 16 years: male = 1.7; female = 1.4
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
  • No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure

Exclusion Criteria:

  • Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
  • Patients with bone marrow failure syndromes
  • Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 365 Days 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 Canada,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03126916
Other Study ID Numbers  ICMJE ANBL1531
NCI-2016-01734 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ANBL1531 ( Other Identifier: Children's Oncology Group )
ANBL1531 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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: Steven DuBois Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date October 2020

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