Skip to content
TriangleGet started
← Study library

NCT03126916 · CITED IN SOURCE DOCUMENTS

Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
RECRUITING
Registry last update
2026-08-25

This phase III trial studies iobenguane I-131 or lorlatinib 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. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916) * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patient must be \>= 365 days and =\< 30 years of age at diagnosis * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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 * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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 * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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 * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45 * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \> 50% by echocardiogram or radionuclide angiogram * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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 * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): See ANBL2131 (NCT06172296) protocol for eligible high-risk neuroblastoma diagnoses * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In addition, all patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) Arm E must have tumors with an ALK aberration * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Given the lack of data with lorlatinib in infant populations, patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) must be \> 1 year of age at time of transfer to ANBL1531 (NCT03126916). Patients \< 1 year of age found to have a qualifying ALK alteration as part of ANBL2131 (NCT06172296) may continue to participate in ANBL2131 (NCT06172296) * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients initially recognized to have high-risk disease must have received no more than one cycle of topotecan/cyclophosphamide either after enrollment to ANBL2131 (NCT06172296) or started emergently prior to enrollment to ANBL2131 (NCT06172296) * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received up to one cycle of intermediate risk chemotherapy prior to initial enrollment to ANBL2131 (NCT06172296) * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In order to facilitate patient transfer and ensure timely distribution of lorlatinib, there are no blood count requirements to meet at time of transfer from ANBL2131 (NCT06172296) to ANBL1531 ((NCT03126916) Arm E. Note the blood count criteria that must be met prior to start of Induction cycle 2 on Arm E. Lorlatinib therapy should start no sooner than day 1 of Induction cycle 2 * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known irreversible grade 2 or greater atrioventricular (AV) block * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Due the potential psychiatric risks from lorlatinib, patients should not have a personal history of a serious psychiatric disorder requiring pharmacologic intervention or severe enough to be considered life-threatening * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution deems 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: * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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) * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with bone marrow failure syndromes * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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 * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Lactating females who plan to breastfeed their infants * FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have previously received treatment with lorlatinib or other ALK inhibitor * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have undergone treatment arm randomization callback or started induction cycle 2 on ANBL2131 (NCT06172296) * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have an INRG Stage L2 tumor without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial) * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients with bone marrow failure syndromes * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): 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 * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Lactating females who plan to breastfeed their infants * PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
healthy Volunteers
false
maximum Age
30 Years
minimum Age
365 Days
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Arm A in detailed description.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspiration and Biopsy
    4. Drug: Carboplatin
    5. Drug: Cisplatin
    6. Procedure: Computed Tomography
    7. Drug: Cyclophosphamide
    8. Drug: Dexrazoxane Hydrochloride
    9. Biological: Dinutuximab
    10. Drug: Doxorubicin Hydrochloride
    11. Procedure: Echocardiography Test
    12. Drug: Etoposide Phosphate
    label
    Arm A (chemotherapy, HSCT, EBRT)
    type
    EXPERIMENTAL
  2. description
    See Arm B in detailed description.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspiration and Biopsy
    4. Drug: Carboplatin
    5. Drug: Cisplatin
    6. Procedure: Computed Tomography
    7. Drug: Cyclophosphamide
    8. Drug: Dexrazoxane Hydrochloride
    9. Biological: Dinutuximab
    10. Drug: Doxorubicin Hydrochloride
    11. Procedure: Echocardiography Test
    12. Drug: Etoposide Phosphate
    label
    Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    type
    EXPERIMENTAL
  3. description
    See Arm C in detailed description. Closed to accrual as of 12/17/20.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspiration and Biopsy
    4. Drug: Busulfan
    5. Drug: Cisplatin
    6. Procedure: Computed Tomography
    7. Drug: Cyclophosphamide
    8. Drug: Dexrazoxane Hydrochloride
    9. Biological: Dinutuximab
    10. Drug: Doxorubicin Hydrochloride
    11. Procedure: Echocardiography Test
    12. Drug: Etoposide Phosphate
    label
    Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    type
    EXPERIMENTAL
  4. description
    See Arm D in detailed description.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspiration and Biopsy
    4. Drug: Carboplatin
    5. Drug: Cisplatin
    6. Procedure: Computed Tomography
    7. Drug: Cyclophosphamide
    8. Drug: Dexrazoxane Hydrochloride
    9. Biological: Dinutuximab
    10. Drug: Doxorubicin Hydrochloride
    11. Drug: Etoposide Phosphate
    12. Radiation: External Beam Radiation Therapy
    label
    Arm D (chemotherapy, HSCT, EBRT)
    type
    EXPERIMENTAL
  5. description
    See Arm E in detailed description.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspiration and Biopsy
    4. Drug: Carboplatin
    5. Drug: Cisplatin
    6. Procedure: Computed Tomography
    7. Drug: Cyclophosphamide
    8. Drug: Dexrazoxane Hydrochloride
    9. Biological: Dinutuximab
    10. Drug: Doxorubicin Hydrochloride
    11. Procedure: Echocardiography Test
    12. Drug: Etoposide Phosphate
    label
    Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Undergo autologous HSCT
    name
    Autologous Hematopoietic Stem Cell Transplantation
    other Names
    1. AHSCT
    2. Autologous
    3. Autologous Hematopoietic Cell Transplantation
    4. Autologous Stem Cell Transplant
    5. Autologous Stem Cell Transplantation
    6. Stem Cell Transplantation, Autologous
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Undergo blood sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Specimen Collection
    type
    PROCEDURE
  3. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Undergo bone marrow aspiration and biopsy
    name
    Bone Marrow Aspiration and Biopsy
    type
    PROCEDURE
  4. arm Group Labels
    1. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    description
    Given IV
    name
    Busulfan
    other Names
    1. 1, 4-Bis[methanesulfonoxy]butane
    2. BUS
    3. Busilvex
    4. Bussulfam
    5. Busulfanum
    6. Busulfex
    7. Busulphan
    8. CB 2041
    9. CB-2041
    10. Glyzophrol
    11. GT 41
    12. GT-41
    type
    DRUG
  5. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm D (chemotherapy, HSCT, EBRT)
    4. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  6. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Cisplatin
    other Names
    1. Abiplatin
    2. Blastolem
    3. Briplatin
    4. CDDP
    5. Cis-diammine-dichloroplatinum
    6. Cis-diamminedichloridoplatinum
    7. Cis-diamminedichloro Platinum (II)
    8. Cis-diamminedichloroplatinum
    9. Cis-dichloroammine Platinum (II)
    10. Cis-platinous Diamine Dichloride
    11. Cis-platinum
    12. Cis-platinum II
    type
    DRUG
  7. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Undergo CT scan
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. Diagnostic CAT Scan
    11. Diagnostic CAT Scan Service Type
    12. tomography
    type
    PROCEDURE
  8. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  9. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Dexrazoxane Hydrochloride
    other Names
    1. Cardioxane
    2. Totect
    3. Zinecard
    type
    DRUG
  10. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Dinutuximab
    other Names
    1. Ch 14.18UTC
    2. Ch14.18
    3. Dinutuximab Beta
    4. MOAB Ch14.18
    5. monoclonal antibody Ch14.18
    6. Qarziba
    7. Unituxin
    type
    BIOLOGICAL
  11. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm D (chemotherapy, HSCT, EBRT)
    5. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 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)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  12. arm Group Labels
    1. Arm A (chemotherapy, HSCT, EBRT)
    2. Arm B (Iobenguane I-131, chemotherapy, HSCT, EBRT)
    3. Arm C (Iobenguane I-131, chemotherapy, BuMel, HSCT, EBRT)
    4. Arm E (lorlatinib, chemotherapy, HSCT, EBRT)
    description
    Undergo echocardiography
    name
    Echocardiography Test
    other Names
    1. EC
    2. Echocardiography
    type
    PROCEDURE
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
750
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Event free survival (EFS) (Arm A, B, D, and E)
    time Frame
    3 years
secondary Outcomes
  1. description
    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.
    measure
    Incidence of adverse events
    time Frame
    Up to 18 months for Arms A-D and 28 months for Arm E
  2. description
    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.
    measure
    EFS (Arm C)
    time Frame
    3 years
  3. description
    OS time is calculated from date of randomization or assignment until death, or until last contact if patient is alive.
    measure
    Overall survival (OS)
    time Frame
    3 years
  4. description
    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).
    measure
    Response rate
    time Frame
    Up to 6 months
Full study description
brief Summary
This phase III trial studies iobenguane I-131 or lorlatinib 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. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib 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 lorlatinib to intensive multimodality therapy for patients with high-risk NBL whose tumors harbor activating point mutations in the ALK gene with a variant allele frequency (VAF) \>= 5% results in superior EFS compared to a contemporaneously treated cohort of patients with tumors without documented ALK activating mutations. SECONDARY OBJECTIVES: I. To describe the toxicities associated with treatment for high-risk NBL with and without the addition of 131I-MIBG or ALK inhibitor therapy. 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 ALK inhibitor therapy. 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 ALK inhibitor therapy. 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 describe end-Induction response, EFS, and OS according to specific ALK mutations, VAF, ALK amplification, the presence of additional genomic findings, or the ALK inhibitor administered. 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 ALK inhibitor therapy 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. XIV. To characterize and describe longitudinal neuropsychological and behavioral effects of high-risk neuroblastoma therapy. XV. To evaluate change in neurobehavioral outcomes over time in patients with neuroblastoma treated with high-risk neuroblastoma therapy plus lorlatinib compared to high-risk therapy alone using parent- or self-report measures of adaptive, executive, and psychosocial functioning. XVI. To characterize the pharmacokinetics and pharmaceutical properties of lorlatinib in children with high-risk neuroblastoma. XVII. To compare the EFS of patients enrolled on Arm E and treated with lorlatinib to the EFS of a historical control comprised of patients with ALK aberrant disease treated on ANBL0532 (NCT00567567). XVIII. To describe the EFS of patients enrolled on Arm E according to lorlatinib exposure during post-consolidation. 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 (CLOSED TO ACCRUAL AS OF SEPTEMBER 28, 2023): 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. Patients undergo echocardiography or multigated acquisition (MUGA) scan, magnetic resonance imaging (MRI) or computed tomography (CT) scan, receive 123I-MIBG and undergo MIBG imaging, bone marrow aspiration and biopsy and blood sample collection throughout the study. ARM B (CLOSED TO ACCRUAL AS OF SEPTEMBER 28, 2023): 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-CONSOLIDATION THERAPY: Patients receive sargramostim, dinutuximab, and isotretinoin as in Arm A-D. Patients undergo echocardiography or MUGA scan, MRI or CT scan, receive 123I-MIGB and undergo MIBG imaging, bone marrow aspiration and biopsy and blood sample collection throughout the study. ARM C (CLOSED TO ACCRUAL AS OF DECEMBER 17, 2020): 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. Patients undergo echocardiography or MUGA scan, MRI or CT scan, receive 123I-MIGB and undergo MIBG imaging, bone marrow aspiration and biopsy and blood sample collection throughout the study. ARM D (CLOSED TO ACCRUAL AS OF SEPTEMBER 28, 2023): Patients receive treatment identical to Arm A. Patients undergo echocardiography or MUGA scan, MRI or CT scan, receive 123I-MIGB and undergo MIBG imaging, bone marrow aspiration and biopsy and blood sample collection throughout the study and may undergo fludeoxyglucose- positron emission tomography (PET) scan on study. 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 lorlatinib PO once daily (QD) starting with cycle 2 and continue until HSCT #1 in the absence of disease progression or unacceptable toxicity. For patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) Arm E, protocol therapy on ANBL1531 (NCT03126916) begins with induction cycle 2 on Arm E (topotecan, cyclophosphamide and lorlatinib). CONSOLIDATION THERAPY: HSCT#1: Patients receive thiotepa and cyclophosphamide as in Arm A. Patients also receive lorlatinib PO QD 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. Lorlatinib is restarted when patient has reached at least day +14 post-HSCT#2 and is able to tolerate enteral medications, provided there is no evidence of disease progression or unacceptable toxicity. RADIATION THERAPY: Patients receive lorlatinib PO QD concurrently with radiation therapy in the absence 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 lorlatinib PO QD on days 15-28 of cycles 2-5 and days 1-28 of cycle 6 in the absence of disease progression or unacceptable toxicity. CONTINUATION THERAPY: Patients receive lorlatinib PO QD on days 1-28. Cycles repeat every 28 days for 18 months in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, MRI or CT scan, undergo MIBG imaging, bone marrow aspiration and biopsy and blood sample collection throughout the study and may undergo PET scan on study. 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.
Source references
references
  1. citation
    Weiss BD, Yanik G, Naranjo A, Zhang FF, Fitzgerald W, Shulkin BL, Parisi MT, Russell H, Grupp S, Pater L, Mattei P, Mosse Y, Lai HA, Jarzembowski JA, Shimada H, Villablanca JG, Giller R, Bagatell R, Park JR, Matthay KK. A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Pediatr Blood Cancer. 2021 Oct;68(10):e29117. doi: 10.1002/pbc.29117. Epub 2021 May 24.
    pmid
    34028986
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-1194d1c05fc522bbd87d
      requested nct id
      NCT03126916
      primary nct id
      NCT03126916
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      d1c4764cefac8f52386eb4980e6ce052c7fa381e5a566d4312d4554760d0b017
      payload sha256
      c24795da27f81b5e9f90dd437e07c60e705c0f81de12749ef1b9bdaeaaa071f3
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-1194d1c05fc522bbd87d
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03126916
      occurrences
      1. context exact
        7988">NCT03107988</a>) and in patients with newly diagnosed high-risk neuroblastoma with activated <em class="gene-name">ALK</em> (COG <a href="/clinicaltrials/NCT03126916">ANBL1531</a>).[<a href="#cit/section_9.42">42</a>] For more information, see the sections on <a href="/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#_214
        end
        992279
        exact text
        NCT03126916
        start
        992268
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/b5dc156ffd41aa11a5.html
      source file sha256
      d1c4764cefac8f52386eb4980e6ce052c7fa381e5a566d4312d4554760d0b017
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:38.429497+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      5b887c191cff63e452682b94a36f2f0fba68c8b5f3d708acb473b5c8b6453db5
      source title
      Childhood Cancer Genomics (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 30, 2025
        datetime
        2025-04-30T12:00:00Z
        display
        April 30, 2025
    2. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-cc1c7c475eea0d8955b1
      requested nct id
      NCT03126916
      primary nct id
      NCT03126916
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      308a08f515ba694b00db3851eb2531e1ed582dada1d1a75d9bb7c00853441821
      payload sha256
      0b7f74c9fd9f6a5e2f23f202d5ffaee814766e7592f75a30a0ae9142f6381d48
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-cc1c7c475eea0d8955b1
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT03126916
      occurrences
      1. context exact
        7988">NCT03107988</a>) and in patients with newly diagnosed high-risk neuroblastoma with activated <em class="gene-name">ALK</em> (COG <a href="/clinicaltrials/NCT03126916">ANBL1531</a>).[<a href="#cit/section_4.42">42</a>] For more information, see the sections on <a href="/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#_214
        end
        253565
        exact text
        NCT03126916
        start
        253554
      2. context exact
        e treatment regimen for children with newly diagnosed high-risk neuroblastoma.[<a href="#cit/section_8.58">58</a>] A randomized trial (<a href="/clinicaltrials/NCT03126916">ANBL1531 [NCT03126916]</a>) incorporating radioactive MIBG therapy into the complex therapy for newly diagnosed high-risk neuroblastoma has completed accrual.
        end
        416727
        exact text
        NCT03126916
        start
        416716
      3. context exact
        children with newly diagnosed high-risk neuroblastoma.[<a href="#cit/section_8.58">58</a>] A randomized trial (<a href="/clinicaltrials/NCT03126916">ANBL1531 [NCT03126916]</a>) incorporating radioactive MIBG therapy into the complex therapy for newly diagnosed high-risk neuroblastoma has completed accrual. </p> <p id="_2
        end
        416750
        exact text
        NCT03126916
        start
        416739
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/d023d406c02e860e22.html
      source file sha256
      308a08f515ba694b00db3851eb2531e1ed582dada1d1a75d9bb7c00853441821
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:09.227808+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      5a0bcb41a33182c1bb316ea92b74ca10701add33aec3077a54a565e6d80cbf53
      source title
      Neuroblastoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 28, 2025
        datetime
        2025-04-28T12:00:00Z
        display
        April 28, 2025

    Preserved source evidence · Independent clinical review pending · Not medical advice