Phase 3 study for people with Neuroblastoma

Reproduced exactly, unedited. Written for researchers rather than for patients.

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