Find-A-Study

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

Purpose

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.

Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
210-562-9149
diazvr@uthscsa.edu

Jaclyn Hung
210-450-5358
hungj@uthscsa.edu

Eligibility

Eligible Ages: Between 365 Days and 30 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)
Condition: Ganglioneuroblastoma
INRG Stage L2
INRG Stage M
INRG Stage MS
Neuroblastoma

Arm Groups

Arm	Description	Intervention
Experimental Arm A (chemotherapy, HSCT, EBRT)	See Arm A in detailed description.	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: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Nov Drug: Dexrazoxane Hydrochloride Given IV Other names: Cardioxane Totect Zinecard 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 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 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 Cista Biological: Sargramostim Given SC Other names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin Drug: Thiotepa Given IV Other names: 1,1'',1''''-Phosphinothioylidynetrisaziridine Girostan N,N'', N''''-Triethylenethiophosphoramide Oncotiotepa STEPA Tepadina TESPA Tespamin Tespamine Th Drug: Vincristine Sulfate Given IV Other names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate Drug: Cisplatin Given IV Other names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum 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 < Biological: Dinutuximab Given IV Other names: Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin Drug: Etoposide Phosphate Given IV Other names: Etopophos Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Topotecan Hydrochloride Given IV Other names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)	See Arm C in detailed description. Closed to accrual as of 12/17/20.	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: Dexrazoxane Hydrochloride Given IV Other names: Cardioxane Totect Zinecard 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 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 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 Cista Biological: Sargramostim Given SC Other names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin Drug: Thiotepa Given IV Other names: 1,1'',1''''-Phosphinothioylidynetrisaziridine Girostan N,N'', N''''-Triethylenethiophosphoramide Oncotiotepa STEPA Tepadina TESPA Tespamin Tespamine Th Drug: Vincristine Sulfate Given IV Other names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate 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 Methanesul Drug: Cisplatin Given IV Other names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum 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 < Biological: Dinutuximab Given IV Other names: Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin Drug: Etoposide Phosphate Given IV Other names: Etopophos 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 Drug: Melphalan Hydrochloride Given IV Other names: Alkeran Alkerana Evomela Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Topotecan Hydrochloride Given IV Other names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental Arm E (crizotinib, chemotherapy, HSCT, EBRT)	See Arm E in detailed description.	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: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Nov Drug: Crizotinib Given PO Other names: MET Tyrosine Kinase Inhibitor PF-02341066 PF-02341066 PF-2341066 Xalkori Drug: Dexrazoxane Hydrochloride Given IV Other names: Cardioxane Totect Zinecard 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 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 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 Cista Biological: Sargramostim Given SC Other names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin Drug: Thiotepa Given IV Other names: 1,1'',1''''-Phosphinothioylidynetrisaziridine Girostan N,N'', N''''-Triethylenethiophosphoramide Oncotiotepa STEPA Tepadina TESPA Tespamin Tespamine Th Drug: Cisplatin Given IV Other names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum 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 < Biological: Dinutuximab Given IV Other names: Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin Drug: Etoposide Phosphate Given IV Other names: Etopophos Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Topotecan Hydrochloride Given IV Other names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)	See Arm B in detailed description.	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: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Nov Drug: Dexrazoxane Hydrochloride Given IV Other names: Cardioxane Totect Zinecard 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 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 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 Cista Biological: Sargramostim Given SC Other names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin Drug: Thiotepa Given IV Other names: 1,1'',1''''-Phosphinothioylidynetrisaziridine Girostan N,N'', N''''-Triethylenethiophosphoramide Oncotiotepa STEPA Tepadina TESPA Tespamin Tespamine Th Drug: Vincristine Sulfate Given IV Other names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate Drug: Cisplatin Given IV Other names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum 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 < Biological: Dinutuximab Given IV Other names: Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin Drug: Etoposide Phosphate Given IV Other names: Etopophos 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 Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Topotecan Hydrochloride Given IV Other names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)
Experimental Arm D (chemotherapy, HSCT, EBRT)	See Arm D in detailed description.	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: Carboplatin Given IV Other names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Nov Drug: Dexrazoxane Hydrochloride Given IV Other names: Cardioxane Totect Zinecard 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 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 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 Cista Biological: Sargramostim Given SC Other names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin Drug: Thiotepa Given IV Other names: 1,1'',1''''-Phosphinothioylidynetrisaziridine Girostan N,N'', N''''-Triethylenethiophosphoramide Oncotiotepa STEPA Tepadina TESPA Tespamin Tespamine Th Drug: Vincristine Sulfate Given IV Other names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate Drug: Cisplatin Given IV Other names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum 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 < Biological: Dinutuximab Given IV Other names: Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin Drug: Etoposide Phosphate Given IV Other names: Etopophos Procedure: Therapeutic Conventional Surgery Undergo standard of care surgery Drug: Topotecan Hydrochloride Given IV Other names: Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral)