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Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT03786783
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies the side effects and how well dinutuximab and sargramostim work with combination chemotherapy in patients with high-risk neuroblastoma undergoing stem cell transplant. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Sargramostim helps the body produce normal infection-fighting white blood cells. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill any cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better in treating patients with high-risk neuroblastoma undergoing stem cell transplant.

Condition or disease Intervention/treatment Phase
Ganglioneuroblastoma High-Risk Neuroblastoma NMYC Gene Amplification Biological: Aldesleukin Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Drug: Dexrazoxane Biological: Dinutuximab Drug: Doxorubicin Drug: Etoposide Radiation: External Beam Radiation Therapy Drug: Isotretinoin Drug: Melphalan Biological: Sargramostim Drug: Thiotepa Drug: Topotecan Drug: Vincristine Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
Biological: Aldesleukin
Given IV
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo ASCT
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

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: 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
Given IV
Other Names:
  • 2, 6-Piperazinedione, 4,4''-propylenedi-, (P)- (8CI)
  • 2,6-Piperazinedione, 4, 4''-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI)
  • ADR-529
  • ICRF-187
  • Razoxane (+)-form
  • Soluble ICRF (L-isomer)

Biological: Dinutuximab
Given IV
Other Names:
  • Ch 14.18UTC
  • Ch14.18
  • MOAB Ch14.18
  • monoclonal antibody Ch14.18
  • Unituxin

Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

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

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
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

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
  • 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
Given IV
Other Names:
  • Hycamptamine
  • Topotecan Lactone

Drug: Vincristine
Given IV
Other Names:
  • LEUROCRISTINE
  • VCR
  • Vincrystine




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 63 days ]
    Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients who experience at least one unacceptable toxicity during cycle 3-5 of induction. Will be assessed by the unacceptable toxicity monitoring rule and by the estimation of the combined toxic death and unacceptable toxicity rate together with a 95% confidence interval (CI).

  2. Proportion of patients who are classified as a "failure" [ Time Frame: Up to 5 years ]
    Feasibility "failures" are defined as patients that do not receive >= 75% of the planned dinutuximab doses during Induction. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients deemed feasibility "failures" during cycle 3-5 of induction. Will be assessed by the monitoring rule and, in addition, by estimation of the feasibility "failure" rate together with a 95% CI. The therapy will be deemed feasible at the specified dose level if the feasibility monitoring rule is not triggered.


Secondary Outcome Measures :
  1. Response rate [ Time Frame: Up to 5 years ]
    Response will be determined using the revised International Neuroblastoma Response Criteria. Response rate will be calculated as the percentage of eligible patients with at least a partial response (PR) or better at the end of Induction and will also be considered in determining whether the regimen is worth further study. Will be calculated, including placement of a 95% CI on the response rate.

  2. Event-free survival [ Time Frame: From study enrollment to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed from baseline up to 5 years ]
    Kaplan-Meier curves will be generated.

  3. Overall survival [ Time Frame: From study enrollment to death, assessed from baseline up to 5 years ]
    Kaplan-Meier curves will be generated.


Other Outcome Measures:
  1. Incidence of naturally occurring anti-glycan antibodies [ Time Frame: Up to 5 years ]
    Will be calculated, including placement of a 95% CI on the incidence. In addition, anti-glycan levels prior to the start of Induction therapy and prior to the start of post-Consolidation therapy will be compared with Wilcoxon's signed-rank test for paired data.

  2. Incidence of natural killer (NK) receptor NKp30 isoforms [ Time Frame: Up to 5 years ]
    Will be assessed by calculating the incidence of NK receptor NKp30 isoforms, including placement of a 95% CI on the incidence.

  3. Response of host factors, including naturally occurring anti-glycan antibodies, KIR/KIR-L genotyping, Fc receptor genotyping, human anti-chimeric antibodies (HACA) [ Time Frame: Up to 5 years ]
    Will be explored with Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous host factors. Both the presence/absence and level of naturally occurring anti-glycan antibodies will be considered. For the KIR/KIR-L analysis, patients will be categorized as either matched or mismatched. Patients will be grouped into one of the three genotype subgroups of Fc receptor genotyping for that analysis. The presence/absence of HACA, anti-idiotype, and pretreatment anti-therapeutic antibodies (PATA)/anti-allotype antibody will be considered for the HACA analysis.

  4. Immune environment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) [ Time Frame: Up to 5 years ]
    The incidence of NK receptor NKp30 isoforms will be calculated, including placement of a 95% CI on each incidence rate. Summary statistics will also be generated for serum cytokine (IL6, CXCL9) levels and gene expression of circulating immune function cells.

  5. Levels of circulating GD2 and tumor cell GD2 expression [ Time Frame: Up to 5 years ]
    Will be assessed by exploring the relationship between response to treatment with > PR (response vs. non- response) with circulating GD2 levels, and GD2 tumor cell expression following therapy with a Wilcoxon rank-sum test. Changes from baseline will also be analyzed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.
  • 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 age or 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 progress 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 as described).
  • 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 (CrCl) or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

    • Age 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
    • Age 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
    • Age 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
    • Age 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
    • Age 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
    • Age 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
    • Age 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
    • Age >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to enrollment).
  • Shortening fraction of >= 27% by echocardiogram (within 7 days prior to enrollment).
  • Ejection fraction of >= 50% by echocardiogram or radionuclide angiogram (within 7 days prior to 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.
  • All patients and/or their parents or legal guardians must sign a written informed consent.
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria:

  • Patients >18 months of age with INRG stage L2, MYCN non-amplified, regardless of additional biologic features.
  • Patients with bone marrow failure syndromes.
  • Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1) are not eligible.
  • Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine, corticosteroids for reasons other than prevention/treatment of allergic reactions, adrenal replacement therapy, etc.) are not eligible.
  • Female patients who are pregnant are ineligible 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 during study therapy and for two months after the last dose of ch14.18 (dinutuximab) are not eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786783


Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Site Public Contact    323-361-4110      
Principal Investigator: Leo Mascarenhas         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Site Public Contact    202-884-2549      
Principal Investigator: Jeffrey S. Dome         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    877-442-3324      
Principal Investigator: Suzanne Shusterman         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Site Public Contact    412-692-8570    jean.tersak@chp.edu   
Principal Investigator: Jean M. Tersak         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Site Public Contact    866-278-5833    info@stjude.org   
Principal Investigator: Sara M. Federico         
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Site Public Contact    801-585-5270      
Principal Investigator: Phillip E. Barnette         
Australia, New South Wales
The Children's Hospital at Westmead Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Site Public Contact    61-2-9845 1400      
Principal Investigator: Bhavna Padhye         
Australia, Victoria
Royal Children's Hospital Recruiting
Parkville, Victoria, Australia, 3052
Contact: Site Public Contact    61 3 9345 5656    Jordan.Hansford@rch.org.au   
Principal Investigator: Bhavna Padhye         
New Zealand
Starship Children's Hospital Recruiting
Grafton, Auckland, New Zealand, 1145
Contact: Site Public Contact    0800 728 436      
Principal Investigator: Andrew C. Wood         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sara M Federico Children's Oncology Group

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03786783     History of Changes
Other Study ID Numbers: NCI-2018-03732
NCI-2018-03732 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ANBL17P1 ( Other Identifier: Childrens Oncology Group )
ANBL17P1 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neuroblastoma
Ganglioneuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aldesleukin
Cisplatin
Cyclophosphamide
Carboplatin
Doxorubicin
Etoposide
Vincristine
Melphalan
Topotecan
Interleukin-2
Etoposide phosphate
Thiotepa
Tretinoin
Mechlorethamine
Dexrazoxane
Ch14.18 monoclonal antibody
Nitrogen Mustard Compounds
3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
Isotretinoin