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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 13, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for children with high-risk neuroblastoma, a type of cancer that affects nerve cells. The researchers want to find out if combining a medicine called dinutuximab with standard chemotherapy, surgery, and stem cell transplantation can improve treatment outcomes. Dinutuximab is an antibody that helps the immune system recognize and attack neuroblastoma cells. Children participating in the trial will be randomly assigned to either receive standard treatment or the new combination of treatment.

To join the trial, children must be under 30 years old and have a newly diagnosed high-risk neuroblastoma. They should not have received other forms of cancer treatment before. Throughout the trial, participants will go through several treatment stages, including chemotherapy, surgery, and possibly stem cell transplantation, followed by additional therapies to help eliminate any remaining cancer cells. Parents and caregivers should know that the trial is currently recruiting participants and that their involvement will include regular check-ups to monitor how well the treatment is working.

Gender

ALL

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