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NCT06172296From ClinicalTrials.govRecruiting

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma

  • Ganglioneuroblastoma, Nodular
  • Neuroblastoma

At a glance

Phase
Phase 3
Study type
Interventional
Sponsor
National Cancer Institute (NCI)
Enrolment target
478
Started
19 April 2024
Main results due
31 December 2029
Study sites
179
Registry updated
24 September 2026

Can you take part?

  • Up to 30 years.
  • Open to any sex.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full eligibility criteria
Inclusion Criteria:

* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* ≤ 30 years at the time of initial diagnosis with high-risk disease
* \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines

  * Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:

    * Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
    * Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
    * Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
    * Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a body surface area (BSA) ≥ 0.25 m\^2
* No prior anti-cancer therapy except as outlined below:

  * Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
  * 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
  * Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex as follows:

  * 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL
  * 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
  * 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
  * 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
  * 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL
  * 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
  * 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
  * ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL

    * The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
  * or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or
  * or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)

    * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\*

  * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* \* Shortening fraction of ≥ 27% by echocardiogram, or

  * Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:

No known contraindication to 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 who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
* Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* 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 prior to enrollment 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
* 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

What this study is about

In the sponsor’s own words, from the registry.

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

Study sites(179)

  • Children's Hospital of Alabama

    Birmingham, Alabama, United States

    Recruiting

  • USA Health Strada Patient Care Center

    Mobile, Alabama, United States

    Recruiting

  • Banner Children's at Desert

    Mesa, Arizona, United States

    Recruiting

  • Phoenix Childrens Hospital

    Phoenix, Arizona, United States

    Recruiting

  • Banner University Medical Center - Tucson

    Tucson, Arizona, United States

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, United States

    Recruiting

  • Kaiser Permanente Downey Medical Center

    Downey, California, United States

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, United States

    Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California, United States

    Recruiting

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, United States

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, United States

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, United States

    Recruiting

  • Mattel Children's Hospital UCLA

    Los Angeles, California, United States

    Recruiting

  • Valley Children's Hospital

    Madera, California, United States

    Recruiting

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, United States

    Recruiting

  • Kaiser Permanente-Oakland

    Oakland, California, United States

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, United States

    Recruiting

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, United States

    Recruiting

  • Sutter Medical Center Sacramento

    Sacramento, California, United States

    Recruiting

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, United States

    Recruiting

  • Rady Children's Hospital - San Diego

    San Diego, California, United States

    Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California, United States

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, United States

    Recruiting

  • Connecticut Children's Medical Center

    Hartford, Connecticut, United States

    Recruiting

  • Yale University

    New Haven, Connecticut, United States

    Recruiting

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, United States

    Recruiting

  • Children's National Medical Center

    Washington D.C., District of Columbia, United States

    Recruiting

  • Broward Health Medical Center

    Fort Lauderdale, Florida, United States

    Recruiting

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, United States

    Recruiting

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, United States

    Recruiting

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, United States

    Recruiting

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, United States

    Recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, United States

    Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida, United States

    Recruiting

  • AdventHealth Orlando

    Orlando, Florida, United States

    Recruiting

  • Arnold Palmer Hospital for Children

    Orlando, Florida, United States

    Recruiting

  • Nemours Children's Hospital

    Orlando, Florida, United States

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, United States

    Recruiting

  • Saint Mary's Medical Center

    West Palm Beach, Florida, United States

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, United States

    Recruiting

  • Memorial Health University Medical Center

    Savannah, Georgia, United States

    Recruiting

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, United States

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, United States

    Recruiting

  • University of Illinois

    Chicago, Illinois, United States

    Recruiting

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, United States

    Recruiting

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois, United States

    Recruiting

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois, United States

    Recruiting

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, United States

    Recruiting

  • Southern Illinois University School of Medicine

    Springfield, Illinois, United States

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, United States

    Recruiting

  • Blank Children's Hospital

    Des Moines, Iowa, United States

    Recruiting

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, United States

    Recruiting

  • Wesley Medical Center

    Wichita, Kansas, United States

    Recruiting

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, United States

    Recruiting

  • Norton Children's Hospital

    Louisville, Kentucky, United States

    Recruiting

  • Children's Hospital New Orleans

    New Orleans, Louisiana, United States

    Recruiting

  • Eastern Maine Medical Center

    Bangor, Maine, United States

    Recruiting

  • Maine Children's Cancer Program

    Scarborough, Maine, United States

    Recruiting

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, United States

    Recruiting

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, United States

    Recruiting

Showing 60 of 179 sites — filter to narrow it down. 176 of the 179 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT06172296. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly | Trialion