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

Study on Investigational Medication with Intensive Therapy for High-Risk Neuroblastoma in Children

M
Marissa Just

Primary Investigator

Enrolling By Invitation
1 years - 30 years
All
Phase 3
1 participants needed
2 Locations

Brief description of study

This phase III trial tests how well adding dinutuximab to induction chemotherapy along with standard of care surgery radiation and stem cell transplantation 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 in greater than normal amounts on some types of cancer cells. This helps cells of the immune system kill the cancer cells. Chemotherapy drugs such as cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, dexrazoxane, doxorubicin, temozolomide, irinotecan and isotretinoin, 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. During induction, chemotherapy and surgery are used to kill and remove as much tumor as possible. During consolidation, very high doses of chemotherapy are given to kill any remaining cancer cells. This chemotherapy also destroys healthy bone marrow, where blood cells are made. A stem cell transplant is a procedure that helps the body make new healthy blood cells to replace the blood cells that may have been harmed by the cancer and/or chemotherapy. Radiation therapy is also given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of induction.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

Event free survival (EFS) [ Time Frame: From time of randomization to first episode of disease relapse or progression post-randomization, first occurrence of a second malignancy, or death, whichever occurs first, up to 12 years ] An intent-to-treat log-rank test comparison of EFS starting from the time of randomization between the standard Children's Oncology Group (COG) induction therapy with or without extended Induction (arm A) and induction chemoimmunotherapy (arm B) with or without extended induction arms will be performed. A final analysis two-sided p-value <0.05 will indicate success. In addition, a sensitivity analysis will be performed consisting of a log-rank test comparison of EFS starting from the time of randomization between patients treated without dinutuximab during induction or extended induction (patients on arm A with GEIR) versus patients treated with dinutuximab during Induction (arm B) who do not receive extended induction.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Neuroblastoma, Ganglioneuroblastoma, Cancer, Riley
  • Age: 1 years - 30 years
  • Gender: All

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 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 (eg, 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 derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the CDC or
  •  a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 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 (eg, 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

This study investigates the effectiveness of adding an investigational medication to standard chemotherapy and other treatments in children with high-risk neuroblastoma. Neuroblastoma is a type of cancer that usually affects young children and develops from immature nerve cells. The investigational medication is a monoclonal antibody that targets a molecule found in high amounts on certain cancer cells, helping the immune system to destroy them.

Participants will undergo various procedures, including chemotherapy, surgery, and radiation, to remove and kill cancer cells. A stem cell transplant may be performed to replace blood cells damaged by treatment. The investigational medication is given during the induction phase of chemotherapy to enhance the treatment effects.

  • Who can participate: Children up to 30 years old with a diagnosis of high-risk neuroblastoma or ganglioneuroblastoma can participate. They must meet specific medical criteria, including having a certain stage of the disease and no prior anti-cancer therapy, except in specified situations.
  • Study details: Participants will receive chemotherapy, surgery, and possibly radiation as part of their treatment. The investigational medication will be administered during the induction phase. This study includes a comparison between standard therapy and therapy with the investigational medication. An inactive substance that looks like the investigational medicine/vaccine but does not contain any medicine may be used for comparison.
Updated on 30 Sep 2025. Study ID: PHO-COG-ANBL2131, 23034
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only